A Multicenter Study to Evaluate the Efficacy and Safety of PEP005 (Ingenol Mebutate) Gel When Used to Treat Actinic Keratoses (AKs) on the Non Head Locations: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Multicenter Study to Evaluate the Efficacy and Safety of PEP005 (Ingenol Mebutate) Gel When Used to Treat Actinic Keratoses (AKs) on the Non Head Locations (NCT00942604), a randomized phase 3 study. The primary outcome is Proportion of Patients With Complete Clearance of Actinic Keratoses (AK) Lesions.

2. Clinical Question

3. Trial Design

The registry record identifies this as a phase 3, randomized, parallel-group study of PEP005 (ingenol mebutate) gel and vehicle gel. Its official title describes a multi-center, randomized, parallel-group, double-blind, vehicle-controlled study in patients with actinic keratoses on non-head locations. The record lists triple masking, while the official title says double-blind; it does not explain the difference in those masking descriptions. The enrollment was 203, and the record marks the study as completed.

The PEP005 group received gel 0.05% once daily for 2 consecutive days. The vehicle group received vehicle gel once daily for 2 consecutive days. The registry lists the study start as 2009-07 and primary completion as 2009-10. The primary outcome was assessed at 57 days, and the population named for that outcome is the intention-to-treat population.

The trial’s primary endpoint was complete clearance in the selected treatment field, defined in the registry as no clinically visible actinic keratoses lesions in that field. Partial clearance was listed as a secondary outcome. The registry record does not report the allocation ratio, the detailed randomization procedure, how masking was maintained, or which roles were masked. The original sample-size justification and planned analysis details beyond the reported analysis are not reported in the registry record. These gaps mean that some design features cannot be evaluated from the record alone.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intention to treat population

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 Proportion of Patients With Complete Clearance of Actinic Keratoses (AK) Lesions, measured over 57 days.

The primary endpoint is the proportion of participants with complete clearance of actinic keratoses lesions in the selected treatment field at 57 days. Complete clearance is defined as no clinically visible AK lesions in that field. The outcome is binary at the participant level: a participant either meets the complete-clearance definition or does not. The registry specifies the intention-to-treat population for this outcome.

A participant-level clearance outcome gives a clinically interpretable summary of whether the defined endpoint was reached, rather than a measure of change in lesion count. It also enables a direct comparison of the proportion meeting the same definition in the two randomized groups. The selected treatment field and the specified assessment time are important parts of the endpoint: the result refers to that field at 57 days, not to all skin locations or to outcomes at other times.

Complete clearance is distinct from partial clearance, which the registry lists as a secondary outcome. The outcome definition does not describe how visible lesions were assessed, how ambiguous assessments were resolved, or how missing assessments were treated. Those details are not reported in the registry record. Consequently, the endpoint can be described from its stated definition, but the record does not permit a full assessment of the procedures used to measure it.

7. Results Posted in the Registry

• PEP005 (Ingenol Mebutate) Gel: 42.0% (42/100) versus 4.9% (5/103) on control; risk difference 37.1 percentage points (95% CI 26.6 to 47.7), risk ratio 8.65 (3.57–20.97); unadjusted two-proportion z-test p = <0.001.

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.

Proportion of Patients With Partial Clearance of Actinic Keratoses (AK) Lesions

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • PEP005 (Ingenol Mebutate) Gel: 55.0% (55/100) versus 6.8% (7/103) on control; risk difference 48.2 percentage points (95% CI 37.3 to 59.1), risk ratio 8.09 (3.87–16.91); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for PEP005 (Ingenol Mebutate) Gel than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry posts one secondary outcome: partial clearance of actinic keratoses lesions at 57 days. Its direction is consistent with the primary outcome’s overall pattern: more participants in the PEP005 group than in the vehicle group met the posted clearance endpoint. This provides a related but distinct view of response, because partial clearance is not the same endpoint as complete clearance. It should be read as supportive context rather than as a substitute for the primary outcome.

The secondary outcome is also binary and has a sponsor-reported Cochran-Mantel-Haenszel test with p=0.001. A separate unadjusted calculation is reported for that outcome, with p < 0.001. The registry does not report an adjusted effect estimate or confidence interval for the sponsor’s test. As with the primary result, the unadjusted comparison and the reported test should be understood as different analyses rather than as identical calculations.

Secondary outcomes usually carry less weight than the primary endpoint because they are not the principal basis for evaluating the study’s stated question. When multiple outcomes are examined, the chance of obtaining a statistically notable result somewhere among them can increase unless the analysis plan addresses multiplicity. The registry record does not report whether a multiplicity procedure was planned or used. This uncertainty makes it inappropriate to interpret the secondary p-value as if it were an independently confirmed primary finding.

The overall pattern across the posted primary and secondary outcomes is directionally aligned, but the record contains only one posted secondary outcome and does not provide a full account of all outcomes measured or analyses conducted. That limitation restricts conclusions about selective reporting and the total number of statistical comparisons. The secondary result adds context to the main endpoint, while its status, multiplicity uncertainty, and lack of detailed analysis information call for a more cautious interpretation.

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

• Proportion of Patients With Partial Clearance of Actinic Keratoses (AK) Lesions

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary and reported as participant counts: each participant either had complete clearance by the stated definition or did not. For binary outcomes, the group proportions describe the fraction of participants meeting the endpoint. The posted counts are 42 of 100 in the PEP005 group and 5 of 103 in the vehicle group. The recalculated comparisons use these group summaries without adjustment.

What does the risk difference express?

The risk difference is the PEP005-group proportion minus the vehicle-group proportion. Its recalculated estimate is 0.371, with a 95% confidence interval from 0.266 to 0.477. A difference on this scale communicates the absolute separation between the observed proportions. It is often straightforward to interpret because it stays in the outcome’s original probability scale. The interval describes a range of values reasonably compatible with the data and the calculation method, subject to the assumptions of that method. It does not account for unreported design or analysis features.

How do relative risk and odds ratio differ?

The relative risk compares the probability of the event between groups as a ratio. Its recalculated estimate is 8.652, with a 95% confidence interval from 3.569 to 20.97. The odds ratio compares the odds of the event rather than the probabilities; its estimate is 14.19, with a 95% confidence interval from 5.314 to 37.91. Both measures indicate the direction and relative scale of the observed contrast, but they answer different mathematical questions. For this reason, they should not be read as if they were the same quantity or substituted for the absolute risk difference.

What does a p-value say?

The recalculated unadjusted p-value is <0.001. The reported Cochran-Mantel-Haenszel analysis gives p=0.001. A p-value describes how unusual data at least as inconsistent with a null hypothesis would be if that hypothesis and the test’s assumptions were true. It is not the probability that the null hypothesis is true, and it does not measure the size, importance, or precision of an effect. A small p-value does not remove concerns about measurement, missing data, multiplicity, or the applicability of the result.

These two p-values arise from different analyses. The registry identifies the sponsor’s method as Cochran-Mantel-Haenszel, while the recalculated p-value is unadjusted and based on the posted group summaries. The record does not describe the strata or other details used in the sponsor’s test. In general, the Cochran-Mantel-Haenszel method can combine evidence across strata while accounting for a grouping variable, but which variables were used and how they were defined are not reported in the registry record. The reported test therefore cannot be fully reconstructed from the posted description.

Why does over-dispersion matter?

Over-dispersion is a general concern for outcomes whose observed variability exceeds what a chosen statistical model expects. For a simple binary endpoint, the central posted information is the number meeting the endpoint and the number assessed in each group. Over-dispersion is more commonly a concern for count or clustered data models, where observations may be more variable or less independent than the model assumes. The registry does not describe a model that accounts for over-dispersion, and the posted primary outcome is reported as participant counts. No claim about an over-dispersion adjustment can therefore be made for this trial.

The recalculated effect estimates and intervals are simple, unadjusted calculations from the posted summaries. The registry record does not identify the confidence-interval construction method for those recalculations. The sponsor’s reported result is a test result rather than a posted effect estimate with an interval, so it gives less information about the magnitude and precision of the sponsor’s own analysis. The calculations are useful for understanding the counts, but they do not replace a complete statistical analysis plan or individual participant data.

11. Confidence Intervals and Precision

Precision concerns how much uncertainty surrounds an estimate. For the primary risk difference, the recalculated estimate is 0.371 and the 95% confidence interval extends from 0.266 to 0.477. The interval is entirely above zero, so the range of values compatible with this calculation excludes no difference. Its width also makes clear that the underlying difference is not known as a single exact value. The interval quantifies sampling uncertainty under the calculation method; it does not capture every possible source of uncertainty in trial conduct or outcome measurement.

The relative risk estimate is 8.652, with a 95% confidence interval from 3.569 to 20.97. The odds ratio estimate is 14.19, with a 95% confidence interval from 5.314 to 37.91. The intervals for these ratio measures are broad on their respective scales. A ratio can have a wide range of compatible values even when the direction of the observed contrast is consistent. Their interpretation also depends on distinguishing risk from odds, and neither ratio communicates the absolute group proportions as directly as the risk difference.

A 95% confidence interval is a statistical procedure that, under repeated use in comparable settings and if its assumptions hold, would cover the true parameter at the stated rate. It is not a statement that there is a 95% probability that this particular interval contains the true value. These intervals are recalculated from posted summaries; the registry does not report corresponding intervals for the sponsor’s Cochran-Mantel-Haenszel analysis.

Precision is not the same as freedom from bias. The interval cannot resolve questions about missing outcomes, endpoint assessment, analysis choices, or generalizability. The registry record does not report enough detail to evaluate those issues fully. The posted counts support a distinct observed contrast, while the interval gives a range of plausible values for the unadjusted difference rather than a guarantee about other settings or future outcomes.

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 sample-size illustrations are planning calculations based on the observed effect, not the trial’s own design justification. For these binary outcomes, the figures are participants per arm, not total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario targets a stated fraction of the observed effect.

The 80% power column means the approximate number of participants per arm that the planning calculation assigns to a design with an 80% chance of detecting the chosen effect under its assumptions. The 90% power column uses a higher target chance of detection, which generally requires more participants for the same effect. These figures describe prospective planning conditions; they do not tell how likely the trial’s observed result was to be detected after the trial ended.

Rows for a smaller fraction of the observed effect use a smaller target difference. Detecting a smaller difference is generally harder, so the illustrations require more participants per arm as the target effect becomes smaller. For example, the primary-outcome planning figures increase from 20 participants per arm for 100% of the observed effect at 80% power to 55 participants per arm for 50% of the observed effect at 80% power. These values are illustrative and depend on the stated assumptions.

This is not observed power. It is a planning illustration derived from the observed effect, and it should not be used as a retrospective measure of the trial’s success or as evidence that the trial was adequately designed. The original sample-size assumptions and justification are not reported in the registry record. The calculations also do not address features absent from the stated assumptions, such as any adjustment for missing data or multiplicity.

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

Worked calculation for this trial

1. Control proportion p₀ = 0.049; treatment proportion p₁ = 0.420; average p̄ = 0.234.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5990 = 1.1740.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5383 = 0.4531.
4. n = (1.1740 + 0.4531)² / (0.3715)² = 19.2, rounded up to 20 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 <- 0.0485436893203883                          # control proportion
p1 <- 0.42                          # 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(942604)
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 = 20 (80% power), 26 (90% power)
 75% of observed effect: n per arm = 30 (80% power), 40 (90% power)
 50% of observed effect: n per arm = 55 (80% power), 72 (90% power)
power.prop.test: 19.2 
Simulated power at n = 20 per arm: 0.857 (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.

14. Analyses Reported by the Sponsor

The registry reports that the sponsor used a Cochran-Mantel-Haenszel analysis to compare the randomized groups for the primary outcome. The reported p-value is 0.001. The registry does not provide a corresponding sponsor effect estimate or confidence interval, and it does not describe the strata used in that analysis. Its magnitude and adjustment details therefore cannot be compared directly with the recalculated effect estimates.

The simple recalculation from the posted counts is unadjusted. It gives a risk difference of 0.371, a relative risk of 8.652, and an odds ratio of 14.19, with the respective confidence intervals described in the statistical interpretation. Its p-value is <0.001. These calculations answer an unadjusted comparison using the available group summaries, whereas the sponsor’s reported test is identified as Cochran-Mantel-Haenszel. Differences between their numerical p-values are not, by themselves, evidence of an error: the methods differ and the registry’s sponsor result is rounded to 0.001.

The recalculation does not take precedence over the sponsor’s analysis in this record; no discrepancy is flagged. The sponsor’s reported analysis remains the registry’s stated trial analysis, while the recalculation offers a separate, transparent description based on the posted counts. Because the registry does not include the adjusted estimate, interval, strata, or full analysis plan, it is not possible to determine how the sponsor’s estimated effect compares in magnitude with the unadjusted contrast.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when multiple outcomes, comparisons, time points, or analyses are tested. Conducting more tests can increase the chance that at least one result appears statistically notable by chance. The registry lists a primary complete-clearance outcome and one secondary partial-clearance outcome, but it does not report a plan for controlling multiplicity or explain how the primary and secondary tests were interpreted together. Whether other outcomes or analyses were considered is not reported in the registry record. The posted p-values should therefore be interpreted with the stated endpoint hierarchy in mind, rather than as a complete account of every possible test.

The primary outcome names the intention-to-treat population, but the registry record does not explain how that population was defined in practice, whether all randomized participants contributed outcome data, or how missing assessments were handled. It does not state whether participants with missing outcome measurements were counted as not having clearance, excluded from the endpoint analysis, or addressed using another method. The arm denominators are posted, but they do not by themselves establish the completeness of follow-up or the handling of missing data.

The record also does not describe whether analyses followed the randomized assignment regardless of treatment received, how protocol deviations were handled, or whether any per-protocol or other analysis populations were examined. These details matter because exclusions or missing outcome data can affect the interpretation of a comparison. The registry’s intention-to-treat label is useful, but it cannot answer those questions without additional analysis details.

The reported Cochran-Mantel-Haenszel method is identified, but the record does not state the strata, the rationale for stratification, or the full statistical plan. It also does not report the confidence interval for that sponsor analysis. As a result, the posted record supports a description of the reported test and the unadjusted recalculation, but not a complete audit of prespecification, missing-data handling, or multiplicity control.

16. 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: abdominal pain (1.0%), chest pain (1.0%), myocardial infarction (1.0%).

For serious adverse events, the registry lists 2 affected participants among 100 at risk in the PEP005 group and 2 among 103 at risk in the vehicle group. The record also lists other adverse events affecting 18 participants among 100 at risk in the PEP005 group and 1 among 103 at risk in the vehicle group. These are counts of participants reported as affected, not a complete description of event severity, timing, duration, or relationship to treatment.

The registry names Abdominal Pain, Chest Pain, and Myocardial infarction among the serious adverse event terms, each with a listed frequency of 1.0%. The record does not provide further detail about individual cases, event timing, attribution, or whether the listed terms account for all serious adverse events. Deaths are not reported in the registry record.

These figures should be read as descriptive safety reporting for the trial, not as proof that an event was caused by a study gel or that an unlisted event did not occur. The record does not provide enough detail to assess comparative safety fully, including the definitions and collection procedures used for adverse events or the duration of safety follow-up.

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

The posted primary data show a higher number of complete-clearance events in the PEP005 group than in the vehicle group at the specified 57-day assessment. The unadjusted risk difference is positive, and its 95% confidence interval excludes zero. The sponsor’s reported test gives p=0.001, while the simple unadjusted recalculation gives p < 0.001. Together, these statistics describe a clear observed difference under the analyses reported, but they do not by themselves establish the clinical importance of that difference or guarantee that it will be reproduced.

The result applies to the trial’s enrolled population, the specified non-head treatment location, the two-day dosing regimen, and the registry’s complete-clearance definition. It does not establish what happens at other assessment times, in other treatment fields, under other regimens, or in populations not represented by the study. The registry record does not provide longer-term outcome information for this endpoint.

A p-value is not the probability that the treatment has no effect, and a confidence interval is not a guarantee that the true effect lies within its bounds. The recalculated interval quantifies statistical uncertainty under its calculation assumptions. It does not address potential bias from missing data, endpoint assessment, or decisions in the analysis plan. The registry does not report enough information to evaluate those issues fully.

The trial record also does not establish the broader balance of benefits and harms. Safety counts are descriptive and do not include all details needed to assess event attribution or follow-up. Nor does the statistical comparison alone determine whether the observed contrast matters for a particular person or setting. The appropriate reading is narrower: the posted trial results describe the relative outcome counts and the uncertainty of an unadjusted comparison within this study.

18. Why This Trial Matters Statistically

This trial illustrates the value of distinguishing an absolute effect from relative measures. The risk difference directly expresses the separation between the observed group proportions, while relative risk and odds ratio express the contrast on ratio scales. Reporting more than one scale can clarify different aspects of a binary endpoint, provided the measures are not mistaken for one another.

It also shows why counts, denominators, estimates, intervals, and p-values answer different questions. Counts describe the observed data; effect estimates quantify the contrast; confidence intervals convey uncertainty; and p-values summarize compatibility with a null hypothesis under a particular test. A statistically small p-value does not replace an estimate of magnitude or a discussion of precision.

The registry’s reported Cochran-Mantel-Haenszel test and the unadjusted recalculation make a useful distinction between a trial’s stated analysis and a calculation based directly on the posted group summaries. The sponsor’s p-value is reported, but the adjusted effect estimate, confidence interval, and details of the test are not. Reading those outputs separately avoids treating them as though they were the same analysis.

Finally, the record demonstrates how registry detail shapes statistical interpretation. The primary population and outcome definition are stated, but multiplicity control, missing-data handling, the original sample-size justification, and key analysis details are not. A careful statistical reading therefore pairs the observed contrast with what the record does and does not establish, rather than allowing a single test result to stand in for the full evidence.

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 registry record does not provide the original sample-size justification or the design assumptions used to choose enrollment. The planning illustrations are based on the observed effect and cannot establish the adequacy of the original design. The reported sponsor analysis lacks a posted effect estimate and confidence interval, and the details of the Cochran-Mantel-Haenszel strata are not reported in the registry record.

Important outcome-process details are also absent. The record does not say how the treatment field was selected, how lesions were assessed, whether outcome assessors were masked, or how missing assessments and protocol deviations were handled. Although the primary population is labeled intention-to-treat, the record does not explain the operational rules used for that analysis. These gaps prevent a full evaluation of measurement and analysis decisions.

The registry lists one secondary outcome, but does not report multiplicity procedures or the complete universe of outcomes and analyses considered. This makes it difficult to assess whether the reported secondary result was prespecified and how it should be weighed among other potential comparisons. The masking information also has two descriptions: triple masking in the registry field and double-blind in the official title; the difference is not explained.

The posted primary comparison is an unadjusted recalculation from aggregate summaries. It cannot account for individual-level characteristics, stratification, or missing-data patterns not described in the record. The available safety reporting is similarly limited: event counts and selected serious-event terms do not provide detail about attribution, timing, duration, or follow-up. These limitations restrict interpretation to the information documented in the registry and should not be replaced with assumptions about trial procedures.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Multicenter Study to Evaluate the Efficacy and Safety of PEP005 (Ingenol Mebutate) Gel When Used to Treat Actinic Keratoses (AKs) on the Non Head Locations — NCT00942604.
• Registry record last updated 2015-03-06; status last verified 2013-11.
• Results first posted 2012-03-19.
• 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.

23. Record Summary

The registry describes a completed, randomized, parallel-group phase 3 study of PEP005 (ingenol mebutate) gel versus vehicle gel for actinic keratoses on non-head locations. Enrollment was 203. The PEP005 regimen was gel 0.05% once daily for 2 consecutive days; the vehicle regimen was once daily for 2 consecutive days.

The primary endpoint was complete clearance in the selected treatment field at 57 days, defined as no clinically visible AK lesions, in the intention-to-treat population. The posted counts were 42 of 100 in the PEP005 group and 5 of 103 in the vehicle group. The sponsor reported a Cochran-Mantel-Haenszel test with p=0.001. An unadjusted recalculation gives a risk difference of 0.371, with a 95% confidence interval from 0.266 to 0.477.

The registry also posts partial clearance as a secondary outcome. Details on the original sample-size justification, multiplicity, missing-data handling, and several analysis procedures are not reported in the registry record.