Prevention of UV-induced Carcinogenic Skin Alterations in Immunosuppressed Solid Organ Transplanted Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Prevention of UV-induced Carcinogenic Skin Alterations in Immunosuppressed Solid Organ Transplanted Patients (NCT01532453), a randomized phase 3 study. The primary outcome is Number of New Clinically Diagnosed Actinic Keratoses or Squamous Cell Carcinomas.

2. Clinical Question

3. Trial Design

The registry describes a Phase 3, randomized, prospective, comparative, multicentre trial with a parallel-group design and no masking. Its title identifies the comparison as MD-3511356 versus standard sun protection measures in immunosuppressed solid organ transplant recipients. The trial status is terminated. The listed enrollment is 244; the primary outcome population description states that 241 patients were randomized, 160 to MD-3511356 and 81 to standard care.

Both groups received detailed information on standardized sun protection measures. The MD-3511356 group additionally received the topical product for use on sun-exposed skin areas once daily in the morning for 24 months. The comparator group used self-provided sunscreen products, with possible individual reimbursement at the investigator’s discretion. The registry identifies MD-3511356 as a device and the comparator as other.

The primary endpoint timeframe is 2 Years. The full analysis set comprised 220 patients: 146 in the MD-3511356 group and 74 in the standard-care group. The safety population included all 241 randomized patients because each received at least one dose of the trial device. The reason for the difference between listed enrollment and the randomized total is not reported in the registry record. Details of allocation procedures, masking beyond the listed absence of masking, and the original sample-size justification are 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.

Before assignment: Of 244 patients enrolled, 3 patients were considered screening failures (003-006, 005-002 and 010-027). Patient 003 006 used forbidden concomitant medication. Patient 005 002 had severe sun damage of the skin, violation of exclusion criterion #5. Patient 010 027 was re-enrolled as Patient 010 029 and later randomized to the MD-3511356 group.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 241 patients were randomized: 160 to the MD 3511356 group and 81 to the standard care group. All 241 randomized patients received at least one dose of trial device and therefore were all included in the safety population. The Full analysis set (FAS) comprised 220 patients: 146 in the MD 3511356 group and 74 in the standard care group.

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 Number of New Clinically Diagnosed Actinic Keratoses or Squamous Cell Carcinomas, measured over 2 Years.

The primary endpoint is the number of new clinically diagnosed actinic keratoses or squamous cell carcinomas over 2 Years. It is a count of newly diagnosed lesions, summarized as a mean and standard deviation in the posted results. The outcome therefore concerns the number of new diagnoses per participant, rather than only whether a participant had at least one new diagnosis.

These lesion types are the conditions named in the trial’s primary question and brief summary. Counting new lesions allows the comparison to reflect differences in the number of diagnoses, including the possibility that participants experience more than one new lesion. The registry also lists a secondary outcome that includes basal cell carcinomas and is expressed as the number of patients with one of the specified new diagnoses. That is a different outcome definition: it concerns whether patients had an event rather than the count of lesions.

The endpoint is clinically relevant to the stated prevention objective, but its interpretation depends on how diagnoses were assessed and how observations were handled over follow-up. Detailed diagnostic procedures, assessment schedules, and the approach to incomplete follow-up are not reported in the registry record.

7. Results Posted in the Registry

• MD-3511356: mean 9.88 versus 11.73 on control; difference -1.85 (95% CI -6.11 to 2.41), standardized effect d = -0.12; z-test p = 0.394.

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.

Number of Patients With New Actinic Keratoses, Squamous Cell Carcinomas or Basal Cell Carcinomas

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • MD-3511356: 77.2% (112/145) versus 83.8% (62/74) on control; risk difference -6.5 percentage points (95% CI -17.4 to 4.3), risk ratio 0.92 (0.81–1.05); unadjusted two-proportion z-test p = 0.257.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between MD-3511356 and the control. The interval gives the range of effects that remain compatible with the data.

The secondary endpoint concerns the number of patients with new actinic keratoses, squamous cell carcinomas, or basal cell carcinomas over 2 Years. It is a patient-level outcome, unlike the primary endpoint’s count of new actinic keratoses or squamous cell carcinomas. The overall pattern in the posted secondary results is directionally similar to the primary group summaries: the MD-3511356 group has a lower reported outcome value than the standard sun protection group. This broad pattern does not establish that the two endpoints measure the same effect.

The secondary outcome adds basal cell carcinomas and counts patients with an event rather than the number of lesions. It therefore complements, rather than duplicates, the primary outcome. Its results should be interpreted as supporting context, not as a substitute for the primary analysis. The registry reports an adjusted odds ratio and an unadjusted recalculated risk difference, which use different statistical measures; their estimates should not be directly equated.

General explanation: when a study assesses multiple outcomes or comparisons, the chance of at least one apparently notable result can increase if no adjustment is made for multiplicity. A prespecified hierarchy or multiplicity adjustment can help control this issue, but the registry’s approach is not reported in the registry record. The secondary result therefore carries less weight than a primary result for confirmatory interpretation, particularly when the statistical plan and multiplicity handling are unavailable. Its p-value should not be treated as independent confirmation of the primary finding.

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

• Number of Patients With New Actinic Keratoses, Squamous Cell Carcinomas or Basal Cell Carcinomas

9. Statistical Interpretation

10. Statistical Methods Explained

What does the unadjusted comparison do?

General explanation: an unadjusted comparison uses the posted summaries for each group without accounting for other variables. For the continuous primary outcome, the recalculation contrasts the group means. The reported mean difference is -1.85, defined as the MD-3511356 mean relative to the standard-care mean. A negative value indicates that the posted mean was lower in the MD-3511356 group. The standard deviations describe variation among participants’ outcome values within each group; they are not confidence intervals for the means.

The recalculation uses the full analysis set sizes listed for the outcome: 74 in the standard-care group and 146 in the MD-3511356 group. The registry describes these as the full analysis set, but does not report the full definition of that population or the handling of missing outcome data. Accordingly, the recalculated estimate should be read as a simple comparison of the posted summary statistics, not as a reproduction of the sponsor’s full statistical analysis.

What does ANCOVA mean in this record?

General explanation: analysis of covariance, or ANCOVA, compares groups while adjusting for covariates included in the model. Adjustment can change an estimated group contrast and its uncertainty compared with a simple unadjusted calculation. The registry reports ANCOVA for the primary comparison and lists p = 0.028, but does not report the adjusted effect estimate, confidence interval, covariates, model specification, or assumptions. Those details are not reported in the registry record, so the reported p-value cannot be used to reconstruct the adjusted comparison.

The secondary outcome also has a registry-reported ANCOVA analysis. The record gives an odds ratio of 0.579, a 95% confidence interval from 0.270 to 1.240, and p < 0.05. The reported confidence interval extends across 1, while the listed p-value is below 0.05. Because the sponsor’s analysis and the recalculation do not align, the sponsor’s own analysis takes precedence; the available registry entries do not explain the apparent tension between the reported interval and p-value.

Why does the endpoint type matter?

General explanation: count outcomes can be analyzed with methods that account for the distribution of counts. A simple mean comparison does not model that distribution or any excess variability. Over-dispersion occurs when count variability is greater than expected under a model’s assumptions; accounting for it can affect standard errors and inference. The posted primary results give means and standard deviations, and the sponsor’s method is named as ANCOVA. Whether over-dispersion was assessed or addressed is not reported in the registry record.

The secondary endpoint is binary at the patient level: it records whether a patient had one or more of the specified new diagnoses. A risk difference compares the observed proportions by subtraction, while an odds ratio compares the odds between groups. These measures use different scales and should not be treated as interchangeable. The registry-reported adjusted odds ratio and the simple recalculation’s risk difference are therefore not the same estimand.

How should p-values be read?

General explanation: a p-value is calculated under a null hypothesis and a set of model assumptions. It measures how unusual the observed data, or data more extreme, would be if that null model were true. It is not the probability that the null hypothesis is true, and it does not quantify the probability that an observed result is due to chance. The recalculated primary p-value is 0.394, while the registry reports 0.028 for its ANCOVA analysis. The two values come from different analyses and should not be blended into a single result.

The registry’s statistical plan, including prespecified covariates, analysis populations for each model, handling of missing observations, and multiplicity procedures, is not reported in the registry record. These omissions limit independent interpretation of the sponsor-reported analyses.

11. Confidence Intervals and Precision

The unadjusted primary mean difference is -1.85, with a 95% confidence interval from -6.107 to 2.407. General explanation: a confidence interval describes a range of effect estimates compatible with the data and the method used, subject to the model’s assumptions. Its width conveys precision: wider intervals leave more uncertainty about the size and direction of the effect.

This interval includes zero, so the unadjusted summary-statistic comparison is compatible with no mean difference as well as with differences in either direction. Its endpoints also allow effects of different magnitudes. The interval does not establish that every value in the range is equally plausible, nor does it address whether any value would be clinically important. No threshold for clinical importance is reported in the registry record.

The registry-reported primary ANCOVA result has a p-value of 0.028 but no adjusted estimate or confidence interval. The precision of the sponsor’s adjusted effect therefore cannot be evaluated from the reported primary analysis details. The unadjusted interval should not be substituted for an interval from that adjusted model.

For the secondary outcome, the registry reports an adjusted odds ratio and confidence interval, while the recalculation is based on a risk difference. Since these are distinct measures, their precision and interpretation are not directly interchangeable. The secondary comparison is also one of multiple outcomes, and the multiplicity approach is not reported in the registry record. These considerations counsel against treating any single interval or p-value as a complete account of uncertainty.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

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

For each stated effect size, the 80% power column gives the number of participants per arm used in the planning illustration to have an 80% chance of detecting that effect under the listed assumptions, if the assumed effect and model are correct. The 90% power column gives the corresponding per-arm planning number for a 90% chance. These are conditional planning calculations, not guarantees about the results of a future study.

The rows describe planning for 100%, 75%, and 50% of the observed effect. As the effect to detect becomes smaller, more participants are needed to distinguish it from random variation under the same assumptions. For the primary outcome, the figures range from 1,101 to 4,403 participants per arm for 80% power and from 1,474 to 5,894 participants per arm for 90% power across those effect assumptions. For the secondary outcome, they range from 575 to 2,151 participants per arm for 80% power and from 769 to 2,878 participants per arm for 90% power.

These calculations are planning illustrations and are not observed power. They do not show the probability that the completed trial’s result is true, and they do not establish the sample size that the original investigators intended to recruit.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.850; pooled standard deviation σ = 15.491.
2. n = 2 × (1.96 + 0.842)² × 15.491² / -1.850² = 1,100.6, rounded up to 1,101 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1.85                      # observed difference in means
sigma <- 15.4906014977298                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1532453)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1,101 (80% power), 1,474 (90% power)
 75% of observed effect: n per arm = 1,957 (80% power), 2,620 (90% power)
 50% of observed effect: n per arm = 4,403 (80% power), 5,894 (90% power)
power.t.test: 1101.6 
Simulated power at n = 1,101 per arm: 0.804 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports ANCOVA for the primary endpoint, with p = 0.028, but gives no adjusted effect estimate or confidence interval. A separate unadjusted recalculation from the posted group means and standard deviations gives a mean difference of -1.85, a 95% confidence interval from -6.107 to 2.407, and p = 0.394. These results differ in statistical conclusion.

The recalculation is a simple comparison of summary statistics and does not reproduce an adjusted model. ANCOVA can account for model covariates, and its result can differ from an unadjusted comparison. The registry does not identify the covariates or provide sufficient model detail to explain the difference. Because the analyses are discrepant, the sponsor’s own analysis takes precedence over the recalculation. That does not remove the limitation that the adjusted estimate and its precision are not reported.

The same distinction matters for the secondary endpoint: the registry reports an adjusted odds ratio, whereas the recalculation uses an unadjusted risk difference. These quantities are on different scales and arise from different analyses. They should be read as separate results, not as competing estimates of precisely the same measure.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and a secondary endpoint, and reports analyses for both. It does not report the protocol’s full analysis plan, a hierarchy among outcomes, or whether any multiplicity adjustment was applied. General explanation: testing multiple outcomes can increase the opportunity for a result to appear statistically notable by chance. Prespecified ordering or adjustment methods can address that concern, but their use cannot be assumed from the registry record.

The primary outcome description states that 241 patients were randomized and that the full analysis set comprised 220 patients: 146 in the MD-3511356 group and 74 in standard care. The safety population included all 241 randomized patients, all of whom received at least one dose of the trial device. The secondary outcome lists 74 standard-care participants and 145 MD-3511356 participants. Reasons for differences in analysis denominators and the handling of missing outcome data are not reported in the registry record.

The registry’s primary analysis is described as ANCOVA, but the covariates, exact model, missing-data method, and analysis assumptions are not reported in the registry record. The endpoint description does not explain whether the count outcome was transformed or modeled in another way. These details matter because analysis choices can affect estimates, standard errors, and p-values.

The study is listed as terminated, but the reason for termination and its relation to recruitment or analysis are not reported in the registry record. Interim analyses, stopping rules, and any changes to the protocol or analysis plan are also not reported in the registry record. Without these details, it is not possible to assess whether the reported analysis populations and methods followed an original prespecified plan.

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: pneumonia (6.2%), biliary sepsis (2.5%), diverticulitis (2.5%), influenza (2.5%), respiratory tract infection (2.5%).

The safety population included 81 participants assigned to standard sun protection measures and 160 assigned to MD-3511356. Serious adverse events affected 29 participants in the standard-care group and 38 in the MD-3511356 group. Other adverse events affected 12 and 11 participants, respectively. These are participant counts, not event counts or rates; the registry’s figures do not establish whether a participant experienced more than one event.

The listed serious adverse event terms include pneumonia (6.2%), biliary sepsis (2.5%), diverticulitis (2.5%), influenza (2.5%), respiratory tract infection (2.5%), and forced expiratory volume decreased (2.5%). The registry record does not provide further context for these percentages in the available entry. Death counts are not reported in the registry record.

General explanation: adverse event counts describe events recorded during a study and do not, by themselves, establish that a study intervention caused them. Interpretation also depends on follow-up, event definitions, exposure, and participant characteristics. Detailed information on these matters is not reported in the registry record. The figures should therefore be read as descriptive safety information rather than as a causal comparison.

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

The posted primary group means are 11.73 new actinic keratoses or squamous cell carcinomas in the standard sun protection group and 9.88 in the MD-3511356 group. The simple unadjusted recalculation estimates a mean difference of -1.85, with a 95% confidence interval from -6.107 to 2.407. This interval includes zero and spans values on either side of no difference, so the unadjusted result is imprecise about the direction and magnitude of the contrast.

The registry also reports an ANCOVA p-value of 0.028 for the primary endpoint. Because this differs from the unadjusted recalculation, the sponsor’s analysis takes precedence. However, the registry does not report the adjusted effect estimate or confidence interval, which prevents a clear assessment of the magnitude and precision of that analysis. A p-value alone does not indicate whether an effect is large, clinically important, or precisely estimated.

The secondary outcome has a lower reported value in the MD-3511356 group than in the standard-care group, but it uses a different endpoint definition and statistical measure. It should be considered in the context of multiple outcomes and the unreported multiplicity plan.

These results do not establish a causal explanation for observed differences, and they do not support medical advice. They describe the registered trial’s group summaries and analyses. Missing information on the statistical plan, diagnostic procedures, incomplete follow-up, and the reasons for termination limits how fully the findings can be assessed.

18. Why This Trial Matters Statistically

This trial illustrates why a reported p-value should be considered alongside an effect estimate and its precision. The primary registry analysis reports p = 0.028, while the unadjusted recalculation gives p = 0.394 and a confidence interval that includes zero. The difference underscores that adjusted and unadjusted analyses can answer related but non-identical questions and may produce different results.

The registry does not report the adjusted primary estimate, interval, covariates, or details of the analysis plan. Without these, readers cannot judge how large the sponsor’s estimated contrast was or how precisely it was estimated. The record also gives different analysis populations for the safety and full analysis sets, and does not report the handling of missing data. Those features matter to the interpretation of both estimates and uncertainty.

The secondary endpoint shows why endpoint definitions matter: the primary outcome counts new lesions, while the secondary outcome counts patients with specified diagnoses and includes basal cell carcinomas. The distinction affects the estimand and the statistical measure used. More generally, a trial record can support a careful description of observed results while leaving important questions about methods and precision unresolved.

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 lists enrollment of 244, while the primary outcome description states that 241 patients were randomized. The reason for the difference is not reported in the registry record. The full analysis set included 220 patients, and the secondary outcome lists 145 MD-3511356 participants. Reasons for these analysis denominators and the handling of missing data are not reported in the registry record.

The primary sponsor analysis is identified as ANCOVA, but the registry does not report its adjusted estimate, confidence interval, covariates, or detailed model specification. The unadjusted recalculation cannot replace that analysis. The difference between the recalculated p-value and the sponsor-reported p-value further limits interpretation from the available details.

The trial is listed as terminated, but its reason for termination is not reported in the registry record. The original sample-size justification, interim analyses, stopping rules, multiplicity plan, and changes to the protocol are also not reported in the registry record. Diagnostic methods, assessment schedules, and the approach to incomplete follow-up are not reported in the registry record.

The trial had no masking according to the registry. The record does not describe whether outcome assessors were otherwise protected from knowledge of group assignment. These limitations affect interpretation of the reported outcomes and do not, by themselves, determine the direction of any possible bias.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Prevention of UV-induced Carcinogenic Skin Alterations in Immunosuppressed Solid Organ Transplanted Patients — NCT01532453.
• Registry record last updated 2016-01-08; status last verified 2015-12.
• Results first posted 2016-01-08.
• 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

NCT01532453 is a terminated, randomized, open-label, parallel-group Phase 3 trial comparing MD-3511356 plus standardized sun protection information with standard sun protection measures in immunosuppressed solid organ transplant recipients. The primary outcome was the number of new clinically diagnosed actinic keratoses or squamous cell carcinomas over 2 Years.

The registry reports 241 randomized patients in the primary population description and a full analysis set of 220. The posted primary means were 11.73 for standard sun protection and 9.88 for MD-3511356. The registry reports an ANCOVA p-value of 0.028, while the simple unadjusted recalculation gives a different result; the sponsor’s analysis takes precedence. Its adjusted effect estimate and confidence interval are not reported in the registry record.

Important details about the analysis plan, missing data, multiplicity, and termination are not reported in the registry record. The results should be interpreted with those limitations in mind.