Metvix PDT Versus Vehicle PDT With Aktilite CL128 Lamp in Patients With Actinic Keratosis on the Face and Scalp: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Metvix PDT Versus Vehicle PDT With Aktilite CL128 Lamp in Patients With Actinic Keratosis on the Face and Scalp (NCT00304239), a randomized phase 3 study. The primary outcome is Participant Complete Response Rate (CRR).

2. Clinical Question

3. Trial Design

This was a Phase 3, randomized, double-blind, parallel-group study described as multicenter and vehicle controlled. Its stated purpose was to compare photodynamic therapy with methyl aminolevulinate cream against photodynamic therapy with vehicle cream, using the Aktilite CL128 LED light source, in participants with multiple actinic keratosis on the face and/or scalp. Galderma R&D is listed as the sponsor. The registry reports enrollment of 131 and a completed study.

The study began on 2006-03-13, and primary completion is recorded as 2007-01-23. Participants assigned to Metvix-PDT received methyl aminolevulinate hydrochloride cream at 160 mg/g on the face and/or scalp for 3 hours on Day 0 and Day 7. Participants assigned to Vehicle-PDT received vehicle cream at the same stated sites and durations. Additional details about the light exposure, treatment preparation, allocation concealment, recruitment sites, or conduct of follow-up are not reported in the registry record.

The primary outcome was participant complete response rate at Week 13, defined as the percentage of participants with complete disappearance of the lesion by investigator clinical assessment, including visual inspection and palpation. The primary outcome population was the intention-to-treat population, defined in the registry as randomized participants for whom any aspect of either treatment was initiated. The posted efficacy denominators are 57 for Metvix-PDT and 58 for Vehicle-PDT. The registry enrollment figure and these outcome denominators describe different record entries; further explanation of their relationship is not reported.

The registry lists lesion complete response rate and participants with at least one treatment-site adverse event as secondary outcomes. Details about prespecified analysis procedures, endpoint assessment beyond the description above, and the original design assumptions are not reported in the registry record. The record lists no analyses in its analysis count, so the posted summary results do not include a detailed account of the sponsor’s statistical model or handling of analysis populations beyond the stated primary population.

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.

Before assignment: A total of 131 participants were enrolled and received treatment in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention-to-treat (ITT) population consisted of all participants that were randomized and for whom any aspect of treatment with either Metvix-PDT or Vehicle-PDT was initiated.

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: The safety population consisted of all participants for whom any kind of treatment was initiated.

6. Primary Endpoint

The registry lists the primary outcome as Participant Complete Response Rate (CRR), measured over At Week 13.

The primary endpoint was participant complete response rate at Week 13. It measures the percentage of participants meeting the study’s definition of complete response: complete disappearance of the lesion as determined by an investigator through visual inspection and palpation. The endpoint is binary at the participant level: a participant either meets the complete-response definition or does not. The registry specifies the intention-to-treat population for this outcome, including randomized participants for whom any aspect of either treatment was initiated.

A response proportion offers a direct way to describe how often the specified clinical assessment was met in each study arm. Comparing the proportions can show the size and direction of the observed difference between the assigned groups. It also makes the outcome easier to interpret than a change in a continuous measurement, because the registry defines a clear response criterion.

The endpoint is limited to the assessment at Week 13. It does not, by itself, measure how quickly a response occurred, whether a response persisted, or whether lesions recurred later. The registry’s definition also relies on investigator assessment, and details about assessment standardization or independent review are not reported in the registry record. The result should therefore be read as a comparison of recorded participant response at the specified time, under the stated definition, rather than as a complete description of longer-term disease course.

7. Results Posted in the Registry

• Metvix-PDT: 68.4% (39/57) versus 6.9% (4/58) on control; risk difference 61.5 percentage points (95% CI 47.8 to 75.2), risk ratio 9.92 (3.79–25.96); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

Binary outcome and response proportion. The primary endpoint is a binary outcome at the participant level: complete response was either recorded or not recorded according to the registry definition. A response proportion is the number of participants meeting that definition relative to the outcome denominator for the arm. The record gives rates of 68.4% for Metvix-PDT and 6.9% for Vehicle-PDT at Week 13. This form of summary is suited to an endpoint defined as whether an individual achieved a specified response by a particular assessment.

Comparing proportions. The comparison between arms can be expressed on an absolute scale or a relative scale. An absolute contrast describes the difference in response proportions; a relative contrast describes how the response frequency in one arm compares with that in the other. The posted comparison reports a risk difference, a risk ratio of 9.921, and an odds ratio of 29.25. The risk ratio compares probabilities, whereas the odds ratio compares odds. They are not interchangeable measures, and the odds ratio can appear especially large when the outcome is relatively uncommon in one arm. Interpreting these measures alongside the observed arm rates helps retain the clinical scale of the outcome.

Confidence intervals. A confidence interval expresses uncertainty in an estimate under the statistical procedure used to construct it. The registry reports 95% confidence intervals for the arm-specific response rates: 54.8% to 80.1% for Metvix-PDT and 1.9% to 16.7% for Vehicle-PDT. In repeated use of a procedure with the same assumptions, confidence intervals would capture the target quantity at the stated rate. For a particular study, the interval is not a probability statement that the fixed true value lies within that specific interval. Its width conveys how much uncertainty remains, while its limits indicate values compatible with the data and procedure.

Unadjusted p-value. The posted comparison reports an unadjusted p-value of <0.001. A p-value measures how surprising data at least as incompatible with the null model would be if that model and the calculation assumptions were correct. It does not measure the probability that the null is true, and it does not measure the chance that the observed result occurred “by chance” in a general sense. The word unadjusted matters: the comparison is not reported as adjusted for other outcomes or covariates. The registry record does not report the sponsor’s full statistical analysis plan or the precise model underlying this comparison.

Recalculated comparison. A simple unadjusted comparison can be recalculated from posted summary statistics, but it is not a substitute for a sponsor analysis that uses participant-level data, prespecified covariates, or documented rules for handling missing observations. The record lists no analyses in its analysis count and does not provide a detailed sponsor model. The posted summary comparison should therefore be understood as a summary-level, unadjusted result rather than evidence about an unreported adjusted analysis. No discrepancy is flagged in the registry record.

Analysis population. The stated primary population is intention to treat, defined as all randomized participants for whom any aspect of treatment with either arm was initiated. In general, an intention-to-treat approach seeks to preserve the comparison created by random assignment and to include participants according to their assigned group. Here, the registry supplies the population definition but does not report the specific handling of participants without a Week 13 assessment, deviations from assigned treatment, or other analysis details. The posted denominators are 57 and 58 for the primary outcome, while the safety risk sets differ. Those denominators should be read as outcome-specific entries, not as a complete explanation of participant flow.

Dispersion and the outcome scale. For a binary proportion, uncertainty depends on the observed event frequency and the amount of information available. A proportion near a boundary can have a different uncertainty pattern from one near the middle of its possible range. Confidence intervals are therefore useful alongside the point estimates, particularly when one arm’s recorded response rate is low. The registry gives intervals for each arm, but the method used to calculate those intervals is not reported in the registry record.

Multiplicity. The registry lists a primary outcome and secondary outcomes, but the statistical plan for interpreting multiple endpoints is not reported in the registry record. When several outcomes are tested, the chance of at least one apparently notable finding can increase unless analyses are planned and interpreted with multiplicity in mind. The primary result can be described as the registered primary comparison; secondary outcomes should not automatically be treated as confirmatory without knowing the prespecified testing strategy. Whether any formal adjustment was planned or performed is not reported.

Limits of summary statistics. Summary rates and comparisons do not reveal the distribution of participant characteristics, site-level variation, adherence, or patterns of missing observations. They also do not identify how consistently the outcome was assessed across sites. Those details may matter when evaluating the robustness and generalizability of a result, but they are not reported in the registry record. Statistical summaries can describe the reported evidence precisely while leaving important design and analysis details unknown.

10. Confidence Intervals and Precision

The point estimates are accompanied by 95% confidence intervals. For Metvix-PDT, the response rate was 68.4%, with an interval from 54.8% to 80.1%. For Vehicle-PDT, the response rate was 6.9%, with an interval from 1.9% to 16.7%. The intervals communicate uncertainty around the arm-specific proportions; they are not guarantees that the true rates fall within those limits, nor do they account for every possible source of uncertainty in study conduct or reporting.

The intervals are fairly broad, particularly in relation to the range of possible response proportions. That breadth is consistent with estimates based on the posted outcome denominators of 57 and 58. The data support a range of plausible values for each arm’s response rate, rather than a perfectly precise rate. The point estimate remains useful as a concise summary, but should be read together with the interval.

Arm-specific intervals answer a different question from a confidence interval for the treatment contrast. The registry’s comparison output includes an interval for the risk difference, but the interval limits are not repeated in this explanation. The distinction matters: overlap or non-overlap between separate arm intervals is not itself a formal test of the between-arm difference. The unadjusted p-value and the comparison estimate address that contrast using their own statistical procedures.

Confidence intervals quantify sampling uncertainty under their construction method. They do not include uncertainty about unreported features such as missing-data handling, outcome assessment consistency, or the analysis plan. The interval method is not reported in the registry record, so its assumptions cannot be assessed from the record alone. Precision should therefore be understood as precision of the posted estimates under the method used, not as a measure of every limitation in the evidence.

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 a report of the trial’s original design calculation. They give participants per arm, not total events. The listed planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning row uses the stated fraction of the observed effect as the effect to detect.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the specified effect under the stated assumptions, if that effect and the assumptions were correct. The 90% power column gives the corresponding planning figure for a 90% chance. These are design calculations, not probabilities that the observed study result is correct. The figures do not establish what the trial was designed to achieve; the original sample-size assumptions are not reported in the registry record.

The rows describe planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. The figures increase as the assumed effect becomes smaller: detecting a smaller difference generally requires more participants, all else being equal. The listed values are 9 and 11 participants per arm for planning around 100% of the observed effect; 15 and 19 for 75%; and 28 and 37 for 50%, for the 80% and 90% power columns respectively.

These figures are not observed power. They are hypothetical planning illustrations using the observed effect as a reference and the stated assumptions. They should not be used to infer that the completed study had a particular probability of success, or that the actual trial’s design followed these calculations.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.069; treatment proportion p₁ = 0.684; average p̄ = 0.377.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6852 = 1.3430.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5294 = 0.4456.
4. n = (1.3430 + 0.4456)² / (0.6152)² = 8.5, rounded up to 9 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
p0 <- 0.0689655172413793                          # control proportion
p1 <- 0.684210526315789                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(304239)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 9 (80% power), 11 (90% power)
 75% of observed effect: n per arm = 15 (80% power), 19 (90% power)
 50% of observed effect: n per arm = 28 (80% power), 37 (90% power)
power.prop.test: 8.5 
Simulated power at n = 9 per arm: 0.863 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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 identifies participant complete response rate at Week 13 as the primary outcome. It also lists lesion complete response rate and the number of participants with at least one treatment-site adverse event as secondary outcomes. The record lists three outcome measures and two secondary outcomes. It does not describe a testing hierarchy, a multiplicity adjustment, or rules for interpreting a collection of endpoint results. Whether the sponsor planned or performed any formal correction for multiple comparisons is not reported in the registry record.

Multiplicity matters because examining several outcomes can increase the chance of at least one result appearing statistically notable under a collection of null hypotheses. A prespecified primary outcome helps distinguish the main comparison from supporting or exploratory outcomes, but it does not answer how secondary results should be interpreted. The posted unadjusted p-value for the primary comparison should not be assumed to incorporate testing across other outcomes.

The primary population is defined as the intention-to-treat population: randomized participants for whom any aspect of either treatment was initiated. The registry reports outcome denominators of 57 for Metvix-PDT and 58 for Vehicle-PDT. It does not report how missing Week 13 assessments were treated, whether any participants were excluded from the response calculation after treatment initiation, or how protocol deviations were handled. Missing-data methods and participant flow by reason are not reported in the registry record.

The safety counts use different risk sets from the primary efficacy denominators. The record does not explain the relationship among those populations in detail. The registry also lists no analyses in its analysis count and does not provide a full statistical analysis plan. Consequently, the available description identifies the primary endpoint and population but leaves important questions about missingness, multiplicity, and implementation of the analysis unresolved.

14. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: basal cell carcinoma left cheek surgery (1.7%), re-surgery and wound suture basal cell carcinoma left cheek (1.7%), knee prothesis right due to arthrosis participants affected / exposed (1.7%), inguinal hernia (1.7%), cerebral concussion (1.4%).

The registry reports serious adverse event figures for participants at risk in each arm. In Metvix-PDT, the serious-event risk set was 73 and 6 participants were affected; in Vehicle-PDT, the risk set was 58 and 3 participants were affected. The record also reports 0 deaths in each arm. These are reported counts and denominators, not calculated rates. The serious-event figures should be read separately from the Week 13 efficacy denominators, which were 57 and 58.

The registry lists serious-event terms including basal cell carcinoma left cheek surgery, re-surgery and wound suture for basal cell carcinoma left cheek, knee prothesis right due to arthrosis, inguinal hernia, cerebral concussion, and hospitalization for coronary cateterization. The listed percentages are 1.7% for the first four terms and 1.4% for the latter two. These are registry entries; the record does not provide enough detail to determine timing, relatedness to study treatment, or whether terms overlap for an individual participant.

Counts alone do not establish that an event was caused by treatment, and the registry’s summary does not provide a complete clinical assessment of each event. The number of participants with other adverse events is also reported: 62 in Metvix-PDT and 34 in Vehicle-PDT, with risk sets of 73 and 58 respectively. The record’s safety summaries should not be interpreted as a treatment recommendation or as proof of absence of risk.

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

The posted results show a higher participant complete response rate at Week 13 in the Metvix-PDT arm than in the Vehicle-PDT arm: 68.4% compared with 6.9%. The reported 95% confidence intervals convey uncertainty around both arm-specific estimates, and the unadjusted comparison reports p < 0.001. Together, these statistics describe a substantial observed separation in the response proportions within this randomized study and the statistical evidence from the posted unadjusted comparison.

That finding has a defined scope. It concerns participants with multiple actinic keratosis on the face and/or scalp, the two registered treatment approaches, the stated assessment definition, and the Week 13 endpoint. It does not describe response durability, recurrence after the assessment, outcomes at other body sites, or results in groups not characterized in the record. The registry does not report longer-term primary response results.

The result also does not settle all questions about analysis. The record defines an intention-to-treat population, but does not describe handling of missing Week 13 assessments or provide the full analysis plan. It lists secondary outcomes without reporting a multiplicity strategy. These omissions limit assessment of how robustly the result reflects the prespecified analysis procedures, even though the posted arm summaries and unadjusted comparison can be described directly.

A statistically small p-value is not a measure of clinical importance, and the relative measures should not replace the arm-specific percentages. The result should not be read as proving that every participant will respond, or that the same observed rates would occur in another setting. It is a summary of the outcomes recorded in this trial, with uncertainty and limitations that remain relevant to interpretation. Nothing in the registry summary alone supports medical advice for an individual.

16. Why This Trial Matters Statistically

This trial illustrates why statistical interpretation benefits from considering an outcome definition, the observed arm proportions, and uncertainty together. Complete response was defined explicitly as disappearance of the lesion on investigator visual inspection and palpation, and the primary assessment was at Week 13. That makes the target of the primary comparison interpretable while also setting a clear boundary on what the result can address.

The contrast is reported both through arm-specific response rates and through relative comparison measures. Relative measures can magnify the apparent scale of a contrast when one arm’s event frequency is low; the absolute response proportions keep the result anchored to the observed participant experience. Confidence intervals add information about the precision of the rates, which a point estimate or p-value alone cannot provide.

The record also highlights the distinction between efficacy and safety populations. The primary outcome denominators differ from the safety risk sets, and the reason for that difference is not reported. Readers therefore need to attend to which population and endpoint each number describes rather than assuming that every summary uses an identical denominator.

Finally, a registered primary result does not answer questions that depend on unreported analysis choices. Missing-data handling, multiplicity procedures, and the original sample-size justification are not reported in the registry record. Recognizing these gaps is part of statistical interpretation, not a reason to disregard the posted findings. The result can be described clearly while remaining appropriately bounded by the record’s detail and follow-up.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry provides a concise trial description but does not report many details needed to assess conduct and analysis fully. Although the study is identified as multicenter, the number and characteristics of sites are not reported in the registry record. Further eligibility criteria and baseline characteristics are also not reported, limiting assessment of how closely the enrolled population represents other groups with actinic keratosis.

The treatment descriptions specify cream strength or vehicle, application sites, and application duration on Day 0 and Day 7. Specific light-delivery settings, procedural details, adherence, and treatment fidelity are not reported. Masking is described as double blind, but who was masked and how the masking was maintained are not reported in the registry record.

The primary endpoint is limited to Week 13. Longer-term response, recurrence, and durability are not reported for this primary result. The outcome depends on investigator assessment by visual inspection and palpation; information about assessor training, assessment standardization, or independent review is not reported.

The registry defines the intention-to-treat population but does not state how missing outcome assessments or protocol deviations were handled. It also does not provide a full statistical analysis plan, the method used for the confidence intervals, or a multiplicity strategy for the primary and secondary outcomes. The original sample-size assumptions are not reported. These limitations concern how completely the record supports evaluation of the design and analysis; they do not change the arm-specific values that are posted.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Metvix PDT Versus Vehicle PDT With Aktilite CL128 Lamp in Patients With Actinic Keratosis on the Face and Scalp — NCT00304239.
• Registry record last updated 2023-07-03; status last verified 2022-08.
• Results first posted 2023-07-03.
• 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

NCT00304239 is a completed Phase 3 randomized, double-blind, parallel-group study sponsored by Galderma R&D. It compared Metvix-PDT with Vehicle-PDT in participants with multiple actinic keratosis on the face and/or scalp. The registry reports enrollment of 131, a start date of 2006-03-13, and primary completion on 2007-01-23.

The primary endpoint was participant complete response rate at Week 13 in the defined intention-to-treat population. The posted rates were 68.4% for Metvix-PDT and 6.9% for Vehicle-PDT, with an unadjusted p-value of <0.001. The record also reports confidence intervals, comparison measures, secondary outcomes, and safety counts.

The registry does not report the full analysis plan, missing-data handling, multiplicity procedures, or original sample-size assumptions. The posted findings should be interpreted within the trial’s stated population, endpoint definition, and follow-up period.