This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Tolerability Comparison Between Differin® Cream 0.1% Versus Differin® Lotion 0.1% in Subjects With Healthy Skin (NCT01046565), a randomized phase 1 study. The primary outcome is Number of Participants Who Were a Success With Regard to Worst Post-baseline Tolerability Assessment Scores in Each Category of the Tolerability Assessments (Erythema, Scaling, Dryness, Stinging/Burning) From Baseline to Week 3..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01046565 |
| Phase | Phase 1 |
| Condition | Skin Manifestations |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Single |
| Enrollment | 75 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Galderma R&D |
| Results posted | Yes |
2. Clinical Question
Population
Subjects with healthy skin were eligible for the comparison. The primary outcome population is identified as per protocol, but the registry record does not report how many participants were included in that population or provide further eligibility details.
Intervention
Differin® Cream 0.1%, identified as adapalene cream 0.1%, was applied once daily to one side of the face for 3 weeks.
Comparator
Differin® Lotion 0.1%, identified as adapalene lotion 0.1%, was applied once daily to the opposite side of the face. The registry describes both formulations as active treatments; it does not describe a placebo comparison.
Primary question
From baseline to week 3, how many participants had a score of 0, defined as success, for each tolerability category: erythema, scaling, dryness, and stinging/burning? The record does not report the counts for either formulation, so the comparison cannot be quantified from the posted primary results.
This is a tolerability question in healthy skin, rather than a comparison of treatment effects on a skin condition. The study summary describes once-daily use for 3 weeks. The primary endpoint focuses on whether the worst post-baseline assessment in each category remained at the best score, not on an average score or change in an overall combined score. A separate secondary outcome is a 6 Question Subject Cosmetic Acceptability Questionnaire. Its results are not reported in the registry record.
3. Trial Design
The registry identifies this as a completed phase 1 study with randomized allocation and single masking. Enrollment was 75. The record lists the sponsor as Galderma R&D, with a start in 2010-01 and primary completion in 2010-02. It gives the study status as completed.
The treatment descriptions specify a split-face comparison: cream was applied to one side of the face and lotion to the opposite side, once daily. This arrangement means that the same participant could receive both formulations, allowing a within-person comparison in principle. However, the registry’s model field identifies the design as parallel. The difference between that model label and the split-face arm descriptions is not resolved in the registry record, so the actual design and analysis structure should not be inferred beyond those recorded details.
The registry does not report which party was masked, how randomization assigned treatments to facial sides, or whether treatment-side assignment was balanced. It also does not report allocation concealment or further procedural details. These omissions matter when assessing whether the treatment comparison was protected from predictable assignment or assessment bias.
The primary outcome population is described as per protocol, but the record does not give its participant count or define the criteria for inclusion in that population. Enrollment therefore should not be treated as the number analyzed for the primary endpoint. The registry lists two outcome measures and no analyses. It describes the primary outcome across multiple tolerability categories, without a single reduced comparison or posted effect estimate. The protocol’s sample-size justification and planned statistical methods 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: Wash-out period up to baseline for topical treatment on the treated area was less than 1 week for corticosteroids and/or 4 weeks for retinoids; for systemic treatment, it was less than 1 week for medications that may have increased photosensitivity and/or 4 weeks for corticosteroids and/or 6 months for retinoids.
Overall Study
| Stage | Differin® Lotion 0.1% and Differin® Cream 0.1% |
|---|---|
| STARTED | 75 |
| COMPLETED | 66 |
| NOT COMPLETED | 9 |
Reasons for not completing this period:
| Reason | Differin® Lotion 0.1% and Differin® Cream 0.1% |
|---|---|
| Adverse Event | 2 |
| Withdrawal by Subject | 7 |
Analysis population for the primary outcome, as defined in the registry: Per protocol
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.
| Characteristic | Unit | Differin® Lotion 0.1% and Differin Cream 0.1% |
|---|---|---|
| Participants analysed | 75 | |
| Age, Continuous | years | 44.75 (SD 13.39) |
| Sex: Female, Male: Female | Participants | 59 |
| Sex: Female, Male: Male | Participants | 16 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants Who Were a Success With Regard to Worst Post-baseline Tolerability Assessment Scores in Each Category of the Tolerability Assessments (Erythema, Scaling, Dryness, Stinging/Burning) From Baseline to Week 3., measured over baseline to week 3.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants classified as successful for each tolerability category from baseline to week 3. Success is defined as having a score of 0. The categories are erythema, scaling, dryness, and stinging/burning. Assessments use a scale from 0 to 4, with 0 described as none and the best score, 1 as mild, 2 as moderate, 3 as severe, and 4 as the worst score.
Using the worst post-baseline assessment makes the endpoint sensitive to the most unfavorable recorded score during the assessment period, rather than to a typical or average score. The separate category counts preserve distinctions between different types of local tolerability findings. A score of 0 is a stringent definition of success for that category; it does not summarize the severity of any nonzero scores or indicate how often assessments were made.
This kind of count can be useful for describing how many participants meet a defined tolerability criterion. It does not, by itself, show the distribution of scores among those who were not successful or the size of any difference between formulations. The registry record does not report the category-specific success counts or an analysis comparing the formulations.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the study question and the endpoint definition, but it does not provide the primary outcome values. It therefore does not show how many participants met the score-0 success definition for cream or lotion in any tolerability category. Without those counts, a numerical comparison, an estimate of difference, and a judgment about precision cannot be made from the posted primary results.
The endpoint is not one combined result. It consists of separate counts for erythema, scaling, dryness, and stinging/burning. A formulation could have different results across these categories, but the record contains no category-level results to examine. The primary outcome description also refers to the worst post-baseline assessment, while the stated timeframe runs from baseline to week 3. The registry does not report the assessment schedule or the handling of participants with assessments missing during that period.
There is an important design detail for interpretation. The treatment descriptions place cream and lotion on opposite sides of the face, which suggests that observations from the two treatment sides may be paired within each participant. The record’s model field, however, labels the model as parallel. These details do not establish which statistical comparison was performed. The registry reports no analyses, so it is not possible to tell whether any reported comparison accounted for within-participant pairing.
No inferential result, such as a confidence interval or p-value, is reported for the primary outcome. General statistical interpretation: a confidence interval describes the uncertainty around an estimated effect, while a p-value addresses how compatible the data are with a specified null model under the analysis assumptions. Neither can be assessed without an estimate, analysis, and its results. The registry also does not report a sample-size justification, so the enrollment figure alone does not establish how precisely the study was designed to estimate tolerability differences.
These absences do not establish that the formulations had the same results, nor do they show that one had better tolerability. They mean that the registry record does not contain the outcome evidence needed to make that comparison. The completed status indicates that the study was recorded as completed; it does not substitute for posted endpoint results.
9. Statistical Methods Explained
The study has a binary primary outcome at the participant level: for each tolerability category, a participant either meets the stated success criterion of a score of 0 or does not. The registry describes the outcome as a number of participants. It does not report the observed counts, an effect estimate, or statistical test results.
What does a participant count convey?
A count makes the endpoint definition concrete: it reports how many participants met the specified criterion. To understand how common success was, readers generally also need the relevant denominator, such as the number assessed for that outcome. For a treatment comparison, an analysis can estimate a difference or another contrast between groups. The registry record does not post the success counts, denominators for the primary outcome, or such an estimate. The enrollment figure should not be substituted for the number analyzed, particularly because the primary population is described as per protocol and its size is not reported.
Why does the split-face description matter?
General statistical explanation: when each participant receives both treatments, the two observations from that participant are related. An analysis that treats those observations as independent can fail to reflect that dependence. A paired analysis uses the within-participant comparison; a parallel-group analysis instead compares participants assigned to separate treatment groups. The registry’s descriptions point in different directions: the arm details specify opposite facial sides, while the model field says parallel. Since no analysis is reported, the approach actually used cannot be established from the record.
What does the scale mean for the endpoint?
The tolerability assessments are recorded on a scale from 0 to 4. The endpoint does not use the full scale to report a mean or a change score. Instead, it counts success when the worst post-baseline score in a category is 0. This makes the outcome a threshold-based binary measure. It can distinguish participants who consistently meet that criterion from those who have any nonzero worst score, but it does not show the severity distribution among participants who fail the criterion.
General statistical explanation: reducing a graded measure to a yes-or-no outcome can make a result easier to interpret against a prespecified threshold, but it discards information about differences within each resulting group. The registry does not state whether the score-0 definition was prespecified in a protocol or analysis plan, so that detail is not reported in the registry record.
What can be learned from an estimate and its uncertainty?
For a binary outcome, an analysis may compare the probability of success between treatments or estimate another contrast. A confidence interval can communicate the range of effects reasonably compatible with the data under the chosen method. A test result may address a null hypothesis, but it does not by itself describe the magnitude or practical importance of an effect. Those interpretations depend on the actual estimate, uncertainty, and analysis assumptions. None of those primary analysis results is reported in the registry record.
General statistical explanation: uncertainty is affected by the amount of information in the data, the outcome frequency, and the design. In a split-face study, accounting for the within-person relationship can affect both the estimate’s uncertainty and the validity of the comparison. The actual amount of information available for this study’s primary analysis is not reported, since the per-protocol participant count and outcome counts are absent.
How should sample-size planning be understood?
A sample-size calculation is a planning exercise based on assumptions about the effect to detect, variability or event frequency, significance level, allocation, and analysis method. It is not evidence that a study achieved a particular level of power after completion. The registry record does not report the trial’s own sample-size justification or assumptions. No sample-size conclusion about the design can therefore be drawn from the enrollment figure alone.
General statistical explanation: a planning calculation can help assess whether a proposed design may estimate an effect with useful precision, but its output depends on the assumptions used. If the observed effect is later used to create a planning illustration, that illustration is not observed power and does not establish the probability that the study detected a true effect. No outcome-based estimate is available in the registry record for such an interpretation.
The registry reports no analyses. As a result, there is no stated primary statistical model, treatment contrast, uncertainty method, or test to explain as the study’s actual analysis. These concepts describe general approaches; they should not be mistaken for methods documented as having been used in this trial.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome includes distinct categories: erythema, scaling, dryness, and stinging/burning. The registry’s note indicates that the primary outcome has several categories or time points and was not reduced to one comparison. This means that the posted record does not define a single summary result for the primary question. It also does not report results for the individual categories.
General statistical explanation: when an analysis makes several comparisons, the chance of obtaining at least one apparently unusual result can increase if each comparison is interpreted without accounting for the set of tests. A statistical plan may specify a primary comparison, a hierarchy, or an adjustment for multiple testing. The registry record does not report a multiplicity strategy, so it is not possible to determine how the study would address multiple category-level comparisons.
The endpoint timeframe is baseline to week 3 and uses the worst post-baseline assessment. The assessment schedule, missing-data rules, and any imputation method are not reported in the registry record. The record also does not say how participants with incomplete assessments would contribute to each category’s count. No conclusions can be drawn about the effect of missing observations on the results.
The primary population is identified as per protocol. The criteria for that population, the number of participants included, and the reasons participants may have been excluded are not reported. The registry does not identify a separate intention-to-treat analysis population or explain how participants were handled in any analysis. Because the analysis count is zero, there are no posted statistical analyses with which to assess these choices.
These reporting gaps limit evaluation of both the result and its robustness. They do not prove that multiplicity, missing data, or population definitions were mishandled; they indicate that the relevant methods and results are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Differin® Lotion 0.1% | 0 | 75 | 0.0% |
| Differin Cream 0.1% | 0 | 75 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Differin® Lotion 0.1% | 0 of 75 |
| Differin Cream 0.1% | 0 of 75 |
The adverse-event record lists 75 participants at risk for serious adverse events in the lotion group and 75 in the cream group. It reports 0 serious adverse events in each group. It also lists 75 participants at risk for other adverse events in each group and reports 0 other adverse events in each group.
These are the posted counts for the categories shown. A count of 0 means that no event in that category is recorded in the registry results for the listed group; it does not describe the range of possible symptoms or indicate how the assessments were collected. The record does not give event terms for these groups beyond reporting no serious-event terms.
The death entries are null rather than a numeric count. A null entry is not the same as a reported count of 0, so the death count is not reported in the registry record. The adverse-event figures also do not replace the primary tolerability endpoint, which assesses erythema, scaling, dryness, and stinging/burning using its own score-based success definition. The posted figures should be read as recorded counts, not as a complete account of all safety information or as evidence about events outside the recorded categories and reporting period.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized comparison of two adapalene formulations used on healthy skin, with a stated treatment period of 3 weeks. It defines a primary tolerability outcome based on whether the worst post-baseline score in each category was 0. These details explain what the study set out to assess, but they do not supply the primary results needed to judge the observed comparison.
The record does not report the number of participants meeting the score-0 criterion for either formulation. It therefore does not establish the size or direction of a difference in erythema, scaling, dryness, or stinging/burning. It also does not report an estimate’s uncertainty or a statistical test. A completed study without posted primary outcome results cannot support a conclusion that the formulations were equivalent, that one was more tolerable, or that there was no difference.
The adverse-event listing records 0 serious adverse events and 0 other adverse events for each group, with 75 at risk in each. These entries are limited to the event categories and information recorded in the registry. The null death entries are not numeric zero counts. The safety listing should not be treated as a substitute for the missing primary endpoint results.
General statistical explanation: absence of a reported difference is not the same as evidence of equivalence. An equivalence conclusion ordinarily depends on a defined margin and an analysis precise enough to assess whether the plausible effects fall within that margin. Such a margin and analysis are not reported in the registry record. Likewise, a lack of reported significance would not establish absence of an effect; in this record, no primary inferential result is posted at all.
The appropriate reading is therefore limited: the study’s recorded purpose, treatment descriptions, endpoint definition, and adverse-event counts can be described, but the posted primary data do not allow a statistical comparison of tolerability results between the two formulations.
13. Why This Trial Matters Statistically
This trial raises a useful design issue for biostatisticians and clinical researchers: its treatment descriptions specify opposite sides of the face, while its registry model field says parallel. In a split-face comparison, each participant may contribute information under both treatments, so the analysis needs to reflect the relationship between measurements from the same person. A parallel-group analysis has a different structure. The record does not resolve which structure was used in the actual analysis.
The endpoint also illustrates how a tolerability outcome can be defined by a threshold rather than by an average score. Success requires a score of 0 for a category, based on the worst post-baseline assessment. This is a clear, interpretable criterion, but a binary count does not preserve the full range of scores. Without category-level results, readers cannot examine how many participants fell short of the threshold or the severity of their scores.
The registry identifies multiple categories in the primary outcome and does not reduce them to one comparison. This makes prespecification and interpretation of the analysis especially relevant. A statistical plan can clarify which contrasts are primary and how multiple comparisons are handled, but that plan is not reported in the registry record.
Finally, the record shows why registration details and posted results serve different purposes. The design and endpoint descriptions tell readers what was intended to be studied; the absence of primary outcome values prevents assessment of what the study observed. The study’s completed status and enrollment figure do not fill that evidence gap. These distinctions are important when interpreting a record without treating design details as results.
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 principal limitation for interpretation is that the registry record does not report the primary outcome counts or an analysis. There is consequently no posted estimate comparing cream and lotion, no uncertainty measure, and no reported test result. The endpoint is described across several tolerability categories, but the record does not give results for any of them.
The study’s structure is not fully clear from the registry. Arm descriptions place the formulations on opposite sides of the face, whereas the model field identifies a parallel design. Randomization is recorded, but the method for assigning treatment to sides and the masked party are not reported. Without an analysis description, it is also unknown whether the comparison accounted for the possibility of paired observations.
The primary endpoint is identified as per protocol, but the participant count and population criteria are not reported. Enrollment was 75, but that figure cannot establish how many participants had usable primary outcome data or met the per-protocol definition. The registry does not report an intention-to-treat analysis, missing-data handling, assessment schedule, or imputation approach.
The outcome’s score scale and success definition are described, but the record does not report whether the definition was prespecified in a protocol or how assessments were conducted. The secondary cosmetic acceptability questionnaire is listed, but its results are not reported. The trial’s sample-size justification, analysis plan, and approach to multiple categories are also not reported in the registry record.
These limitations concern what can be evaluated from the registry, not proof that the study procedures were inadequate. They restrict conclusions about the precision, completeness, and analysis of the tolerability comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Tolerability Comparison Between Differin® Cream 0.1% Versus Differin® Lotion 0.1% in Subjects With Healthy Skin — NCT01046565.
- Registry record last updated 2022-08-25; status last verified 2011-11.
- Results first posted 2011-05-02.
- 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.
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18. Record Summary
This completed phase 1 randomized study enrolled 75 subjects with healthy skin to compare Differin® Cream 0.1% with Differin® Lotion 0.1%. The treatment descriptions specify once-daily application to opposite sides of the face for 3 weeks. The registry records single masking and a parallel model, although the split-face descriptions leave the analysis structure unclear.
The primary endpoint counts participants whose worst post-baseline score was 0 in each tolerability category from baseline to week 3. The primary population is per protocol. The registry lists a 6 Question Subject Cosmetic Acceptability Questionnaire as a secondary outcome. It reports no analyses, and the primary outcome counts and secondary questionnaire results are not reported in the registry record.
For both treatment groups, the record lists 0 serious adverse events and 0 other adverse events, with 75 at risk for each category. Death entries are null, not numeric zero counts. The posted record therefore describes the study design, endpoints, and event counts, but does not provide the primary results needed to compare tolerability.