Potential Impact of Patient Vitamin D Status in AK Response to MAL-PDT: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Potential Impact of Patient Vitamin D Status in AK Response to MAL-PDT (NCT02878382), a randomized na study. The primary outcome is Changes From Baseline in Actinic Keratosis - Lesion Base Count..

2. Clinical Question

The study rationale concerns the possibility that pretreatment could influence response to photodynamic therapy. The registry explains that thicker lesions may have reduced response, potentially associated with insufficient accumulation of the photosensitizer PpIX, and presents vitamin D as a proposed way to stimulate PpIX production. However, the intervention listed is calcipotriol-assisted MAL-PDT; the record does not report a measured patient vitamin D status result or show how such status relates to lesion counts.

The clinical question therefore has a specific treatment comparison and a defined lesion-count outcome, but the posted record does not provide the values needed to determine the observed direction, size, or precision of any difference. The trial description alone cannot establish whether either approach produced a greater reduction in lesions.

3. Trial Design

The registry describes a randomized, single-masked, parallel study with enrollment of 20 participants. Its status is completed. The study start is listed as 2016-10 and primary completion as 2017-01. The phase is recorded as NA. The sponsor is the University of Sao Paulo.

The two interventions are conventional MAL-PDT and calcipotriol-assisted MAL-PDT. The conventional treatment is described as methylaminolevulinate 16% topical PDT on one half of the scalp with multiple actinic keratoses. The calcipotriol-assisted approach adds ointment 50 mcg/g once a day for 15 consecutive days to one half of the scalp before conventional topical PDT. The description of treatment on scalp halves is important to understanding the comparison, but the registry also classifies the model as parallel. It does not explain whether randomization assigned participants to groups, sides of the scalp, or another unit, nor does it clarify how the treatment descriptions map to the parallel-model label.

Single masking is recorded, but the identity of the masked party or parties and the practical masking procedures are not reported in the registry record. The method used to generate the random allocation sequence, allocation concealment, and any stratification are also not reported. These details matter because they help readers assess whether assignment could be anticipated and whether the comparison groups were formed as intended.

The primary outcome is described as change from baseline in actinic keratosis lesion count, with observations intended at 90 days, 180 days, and 12 months after PDT. The outcome description gives baseline counts of 290 lesions on the calcipotriol-assisted side and 284 on the conventional side. It says that follow-up counts include uncleared lesions and newly emerged lesions in the treated field. Secondary outcomes listed are pain scores immediately after illumination and change from baseline in PPIX fluorescence intensity.

Although the registry gives a completed status and an enrollment count, it does not report participant flow, the number analyzed at each follow-up, baseline participant characteristics, or protocol deviations. It also does not report the statistical analysis plan or a clear statement of the unit of analysis. Those omissions limit assessment of how closely the planned comparison can be reconstructed from 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.

Population: 20 male patients were selected and enrolled in the study. The eligibility criteria were: male sex, minimum age of 50 years old, at least 6 AKs symmetrically distributed on the scalp, only AKs grades I and II and immunocompetent patients. To receive either Conventional PDT or CAL-PDT on the allocated side of the scalp (right or left)

6. Primary Endpoint

The registry lists the primary outcome as Changes From Baseline in Actinic Keratosis - Lesion Base Count., measured over Change from baseline, 90 days, 180 days and 12 months after the PDT.

The primary endpoint concerns actinic keratosis lesion counts on the scalp. Lesion counts are a direct measure of the number of lesions in the treated field, and tracking them over follow-up can describe whether the count changed after treatment. The registry title for the endpoint refers to changes from baseline, while its description says that the values represent mean numbers of lesions on each side at 3, 6, and 12 months after intervention. It does not spell out the exact calculation used to turn those follow-up counts into a change-from-baseline value.

The registry defines the count to include lesions that have not cleared and newly emerged lesions in the treated field. This means the endpoint is not limited to persistence of lesions documented at baseline: the observed count can also reflect new lesions appearing during follow-up. That definition can make the measure relevant to the overall lesion burden in the field, but it does not separately distinguish persistence from new emergence in the description.

Baseline counts are reported as 290 on the calcipotriol-assisted side and 284 on the conventional side. The record does not report the follow-up means, standard deviations, changes, or a comparison between the sides. It also does not report how lesions were assessed, whether assessors were masked, or how missing lesion counts were handled. Consequently, the endpoint is described, but the posted record does not allow readers to quantify its observed change or precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry characterizes the primary measure as continuous, with the result type expressed as a mean and standard deviation. A mean summarizes the average lesion count in the observations being analyzed. A standard deviation describes variation among those observations; it is not the same as uncertainty in the estimated mean. The registry does not provide the mean or standard deviation values at follow-up, so these summaries cannot be used to assess the observed data.

What would a treatment contrast represent?

General statistical explanation: a treatment contrast compares outcome summaries under the competing approaches. For a continuous endpoint such as lesion count, an analysis might compare mean counts or mean changes, but the choice depends on the planned estimand and design. The registry labels the primary endpoint as a change from baseline, yet its description also calls the displayed values mean lesion counts at follow-up. It does not state the exact contrast or calculation used. No numerical contrast is reported, so neither its direction nor magnitude can be described.

Study structure affects the appropriate analysis. The record calls the study randomized and parallel, but describes each treatment as being applied to one half of the scalp. If observations from two scalp sides belong to the same participant, they may be correlated; a statistical analysis should reflect that dependence rather than treating all side-level measurements as unrelated. If participants rather than scalp sides were assigned as parallel groups, a different structure may apply. The registry record does not resolve the allocation unit or state the analysis unit, so it is not possible to verify which approach was used.

Why does uncertainty matter?

General statistical explanation: a confidence interval conveys uncertainty around an estimated contrast. A narrow interval indicates greater precision under the model, while a wide interval indicates less precision. An interval that includes values on both sides of no difference may be compatible with several interpretations, depending on its width and on what differences matter. The record does not report an interval or the outcome summaries needed to reconstruct one. No new estimate can be calculated from the baseline lesion totals alone.

General statistical explanation: a p-value is a measure of how unusual data at least as incompatible with a null hypothesis would be if that hypothesis and the analysis assumptions held. It is not the probability that the null hypothesis is true and does not measure effect size. The registry does not report a test result, test specification, or model, so no significance conclusion is available.

How should planning calculations be read?

The registry describes a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect, and that non-time-to-event planning quantities are expressed as participants per arm for 80% power. These assumptions describe an illustrative calculation, not the trial's original design justification. The record does not report a sample-size justification for the study's enrollment of 20 participants, and the numerical planning results are not reported in the registry record.

General statistical explanation: a planning calculation asks how much information would be needed to detect a specified effect under stated assumptions. It is not an estimate of the probability that the completed trial detected an effect, and it is not evidence that an observed effect is real. A calculation based on an effect observed in a study can be especially dependent on that estimate, so the assumptions and uncertainty in the observed effect matter. Any such planning quantities should be read as illustrations rather than as observed power or as a retrospective verdict on the trial.

Over-dispersion is a general concern when outcome variability exceeds what a chosen statistical model assumes. If a model understates variability, standard errors can be too small and confidence intervals can be too narrow. Lesion counts may have features that require careful modeling, but the registry does not report the distributional assessment or model used. There is no basis in the record to say whether over-dispersion was present or how it was handled.

The record also does not report whether the analysis adjusted for baseline lesion counts, how repeated follow-up measurements were handled, how missing observations were treated, or whether any sensitivity analyses were conducted. These are not minor details that can be inferred from the endpoint label. Without an analysis plan and numerical findings, readers can understand the intended outcome and design rationale but cannot reproduce or evaluate the statistical result.

10. Multiplicity, Missing Data and Analysis Populations

The primary outcome description includes follow-up at 90 days, 180 days, and 12 months. The registry also lists secondary outcomes for pain scores immediately after illumination and change from baseline in PPIX fluorescence intensity. It reports 4 outcome measures and 3 analyses. These counts do not, by themselves, reveal how many statistical hypotheses were tested, which time point was primary for inference, or whether any adjustment for multiple comparisons was planned.

General statistical explanation: when several outcomes, time points, or subgroup comparisons are tested, the chance of obtaining at least one apparently unusual result can increase if each is interpreted without accounting for the set of tests. A prespecified hierarchy, adjustment procedure, or clearly designated primary comparison can help readers understand how to interpret multiple findings. Such procedures and a full analysis plan are not reported in the registry record. The primary outcome spans multiple time points and is not reduced to a single comparison in the registry description.

Missing-data handling is also not reported. The record does not state how many participants contributed data at each follow-up, how incomplete observations were addressed, or whether reasons for missing measurements were recorded. General statistical explanation: missing observations can affect interpretation if the participants with available measurements differ systematically from those without them. The effect depends on the amount and pattern of missingness and on the analysis assumptions; none can be assessed from the information in the record.

Analysis populations are not described. The registry does not say whether all randomized participants were analyzed according to assignment, whether a per-protocol population was defined, or whether exclusions occurred. It also does not explain how participant-level and scalp-side observations were handled. Because the design label and treatment descriptions leave the allocation and analysis units unclear, this omission further limits assessment of multiplicity, missingness, and the intended estimand.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 3% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports no serious adverse events among 20 participants at risk in the calcipotriol-assisted MAL-PDT group and none among 20 at risk in the conventional MAL-PDT group. It separately reports other adverse events affecting 15 participants in the calcipotriol-assisted group and 12 in the conventional group, with 20 at risk in each group. These are the posted counts, not a formal comparison of safety between approaches.

The record does not report the definitions used for serious and other adverse events, the event collection period, severity or relatedness assessments, or how recurrent events were counted. It also does not report deaths; death counts are not reported in the registry record. The numbers therefore should not be read as a complete description of the types, timing, or clinical significance of events.

General statistical explanation: an observed count of zero serious events does not establish that the underlying risk is zero. With limited enrollment, uncommon events may not occur among those observed even when a population risk exists. Conversely, the counts of other events cannot be interpreted as evidence of a difference without a specified analysis and enough contextual information about event definitions and follow-up.

The adverse-event figures provide a limited descriptive account for the enrolled groups. They do not establish comparative safety, and they should be considered alongside the incomplete reporting of event characteristics and follow-up.

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

The record makes clear what clinical comparison was intended: conventional MAL-PDT versus calcipotriol-assisted MAL-PDT for scalp actinic keratoses. It describes the proposed pretreatment, the baseline lesion totals, follow-up timing, and the inclusion of uncleared and newly emerged lesions in the count. It also records adverse-event counts and the completed status of the study. Those details help define the research question, but they do not disclose the primary outcome findings.

Without follow-up lesion-count results, a treatment contrast, and an uncertainty estimate, the registry cannot show whether lesion counts changed differently between approaches. It cannot show how large any difference was, how precise an estimate may have been, or whether the findings were compatible with no difference. The absence of posted estimates must not be interpreted as proof of no effect or as proof that the approaches are equivalent.

The study description also does not establish that patient vitamin D status modified response. Although the title and rationale mention vitamin D, the listed intervention is calcipotriol-assisted MAL-PDT, and the registry does not report vitamin D measurements or a result relating vitamin D status to lesion counts. The proposed biological rationale is not itself a clinical outcome.

General statistical explanation: results are most informative when the estimate, its uncertainty, the analysis population, and the outcome definition are considered together. A small or imprecise estimate may leave substantial uncertainty, while an apparently precise estimate can still be affected by bias, missing data, or a mismatch between analysis and design. Here, the registry does not report the numerical efficacy results or enough analytic detail to assess these possibilities.

The adverse-event counts are descriptive and do not establish comparative safety. Enrollment of 20 participants also does not tell readers how complete follow-up was or how many observations entered each analysis. The appropriate conclusion is therefore narrow: the record documents a randomized study design and specified outcomes, but does not provide enough result information to support a conclusion about comparative efficacy or safety.

13. Why This Trial Matters Statistically

This study raises statistical questions that are important whenever interventions are compared using repeated lesion counts. The registry defines the endpoint to include both lesions that remain and new lesions in the treated field. That definition affects what the measure represents: it is a count of total lesion burden at follow-up, not simply a tally of baseline lesions that persisted. Distinguishing persistence from new emergence could add useful context, but separate results are not reported.

The record also presents a design-description issue with consequences for analysis. It classifies the study as parallel and randomized, while the treatment descriptions assign each approach to one half of the scalp. If the two sides were measured within each participant, the side-to-side comparison may involve paired observations. If the randomization unit was different, the appropriate analysis could differ. Since the allocation and analysis units are not clarified, readers cannot determine how the design should be represented statistically.

Repeated outcome assessment at 90 days, 180 days, and 12 months creates choices about the primary time point and treatment of repeated measurements. The registry gives no statistical plan explaining those choices or whether multiple comparisons were addressed. General statistical explanation: prespecifying the main contrast and analysis helps prevent emphasis from shifting among time points after results are known. Without those details and the numerical results, it is not possible to judge the strength or robustness of evidence.

The registry's planning description also illustrates why planning calculations should be kept separate from trial results. It states assumptions for a normal-approximation illustration based on an observed effect, but does not report a design justification for enrollment of 20. A planning illustration cannot substitute for a treatment estimate, and it does not describe the probability that the completed study detected an effect.

The statistical importance of this record lies in the questions it raises about outcome definition, paired versus parallel structure, repeated measurements, multiplicity, and transparent reporting. The absence of posted efficacy estimates prevents those questions from being resolved for this study, but makes clear which information is necessary for a defensible interpretation.

14. Limitations

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

The most consequential limitation of the registry record is that it does not report the primary outcome values. Follow-up means and standard deviations, changes from baseline, a treatment contrast, and uncertainty estimates are all not reported in the registry record. The stated baseline lesion counts alone cannot establish what happened after treatment.

Design details are incomplete. The record calls the study parallel, yet describes each intervention as applied to a half of the scalp. It does not explain the randomization unit, the unit used for analysis, or whether the sides were analyzed as paired observations. The meaning and implementation of single masking are also not reported, nor are the sequence-generation or allocation-concealment methods.

The endpoint description has some ambiguity. It calls the primary outcome a change from baseline but describes the values as mean lesion counts at follow-up. It does not state the precise change calculation or separate lesions that persisted from newly emerged lesions. The method of lesion assessment and any assessor masking are not reported.

Participant flow, baseline participant characteristics, follow-up completeness, missing-data methods, analysis populations, and protocol deviations are not reported. The record lists secondary outcomes but does not provide their numerical results or explain the multiplicity strategy. It also does not give the statistical model or state whether baseline counts and repeated observations were accounted for.

The adverse-event section supplies counts but not event definitions, timing, severity, relatedness, or a detailed account of deaths; death counts are not reported in the registry record. Finally, although the rationale and title refer to patient vitamin D status, the record does not report a measurement or analysis of patient vitamin D status. Together, these limitations restrict interpretation to the trial's stated design and planned outcomes rather than its comparative findings.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Potential Impact of Patient Vitamin D Status in AK Response to MAL-PDT — NCT02878382.
• Registry record last updated 2020-08-04; status last verified 2020-07.
• Results first posted 2020-08-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a completed randomized, single-masked study with a parallel model and enrollment of 20 participants. It compares conventional MAL-PDT with calcipotriol-assisted MAL-PDT for scalp actinic keratosis. The calcipotriol-assisted regimen is described as ointment 50 mcg/g once a day for 15 consecutive days before conventional topical PDT. The study start is 2016-10 and primary completion is 2017-01.

The primary outcome concerns change from baseline in lesion count, with follow-up described at 90 days, 180 days, and 12 months. Baseline counts are 290 on the calcipotriol-assisted side and 284 on the conventional side; the definition includes uncleared and newly emerged lesions. Secondary outcomes include pain after illumination and change in PPIX fluorescence intensity.

The registry reports adverse-event counts, but does not report the primary outcome results, a treatment-effect estimate, or its precision. The allocation and analysis units, missing-data approach, and detailed statistical plan are not reported in the registry record. Consequently, the record establishes the intended comparison but does not support a conclusion about comparative efficacy or safety.