Atralin Gel for the Treatment of Rosacea: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Atralin Gel for the Treatment of Rosacea (NCT01125930), a randomized phase 3 study. The primary outcome is Severity of Erythematotelangiectatic Rosacea Signs: Redness (Non Transient Erythema).

2. Clinical Question

The trial summary frames the clinical question around whether topical tretinoin might improve ETR, a rosacea subtype described as involving facial redness, frequent flushing, topical sensitivity, and prominent blood vessels. The rationale in the summary is that sun-related skin damage may play a role in ETR and that tretinoin is known to improve photodamage. These statements describe the trial's rationale, not a result of the trial.

The registry lists the primary outcome as severity of ETR signs, with redness identified as non-transient erythema. Its description also names telangiectasia, facial edema, and dry skin as signs considered. The outcome is expressed as a number of participants, but the record does not give the exact scoring rule or the threshold used to determine which participants count in any category.

The intervention schedules included possible adjustment according to irritation at follow-up. The record does not report the actual application frequency participants followed, the number who changed schedules, or adherence by treatment group. It also does not provide a primary-outcome estimate comparing the groups. Consequently, the stated clinical question can be described, but the posted results do not establish the direction or precision of a treatment contrast.

3. Trial Design

This was a randomized, triple-masked, parallel-group phase 3 trial. The registry lists enrollment of 68 and identifies Atralin gel and vehicle gel as the two interventions. Randomization generally aims to make treatment groups comparable at the start of a trial, while masking is intended to limit the influence of treatment knowledge on participant behavior, care, or outcome assessment. Those are general purposes; the record does not specify the randomization procedure or which parties were masked.

The planned comparison was topical Atralin gel against vehicle gel. The vehicle was described as a topical gel without active drug. Both arms had an initial schedule of application to the face 3 times per week, with possible increases in frequency if no irritation was observed at follow-up and a maximum frequency of once daily. The arm descriptions are incomplete in the registry record, so additional instructions cannot be established from the available descriptions.

The registry lists a study start of 2010-05 and a primary completion date of 2013-01. The study status is terminated. The reason for termination, the date of termination, and whether termination was related to safety, recruitment, resources, or another issue are not reported in the registry record. The summary says Atralin was to be used for up to 46 weeks, while the primary outcome timeframe is 24 weeks. The record does not explain the relationship between that intended use period and the primary assessment.

The primary outcome population is described using the labels Last Observation Carried Forward (LOCF) and Complete-Case Intent-to-Treat (ITT). The record does not give group-specific analysis counts or a detailed account of how those populations were constructed. It lists Quality of Life, Photodamage, ocular manifestations, phymatous changes, papulopustular signs, molecular markers of inflammation, molecular evidence of photodamage, and non-transient erythema among secondary outcomes.

The registry lists 26 outcome measures and 82 analyses. These counts indicate that the record contains a broad set of outcome and analysis entries, but do not on their own describe which comparisons were planned, which were performed, or how statistical testing was organized. A detailed protocol or statistical analysis plan is 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Last Observation Carried Forward (LOCF), Complete-Case Intent-to-Treat (ITT) 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 Severity of Erythematotelangiectatic Rosacea Signs: Redness (Non Transient Erythema), measured over 24 weeks.

The primary endpoint is titled “Severity of Erythematotelangiectatic Rosacea Signs: Redness (Non Transient Erythema)” and has a timeframe of 24 weeks. The registry describes the measure as taking account of redness, telangiectasia, facial edema, and dry skin. The recorded unit is participants and the parameter is a number. This indicates a participant count rather than a continuous measurement such as a score, but the record does not specify the rule used to assign participants to outcome categories.

Redness is a clinically relevant feature to assess in a trial focused on ETR because the trial summary describes this subtype as involving facial redness and frequent flushing. In general, a prespecified endpoint gives a trial a defined outcome for evaluating its main question. A clear endpoint definition also helps readers understand what a treatment-group contrast represents and how well the measure reflects the condition of interest.

The registry title emphasizes non-transient redness, while the endpoint description lists several signs that are considered. The exact scoring instrument, category definitions, threshold for a participant to count as improved or affected, and handling of changes from baseline are not reported in the registry record. It is therefore not possible to infer from the endpoint description alone whether the reported count represents participants with a particular severity, a change, or another classification.

The endpoint is associated with a 24-week timeframe, but the record does not provide a single primary-outcome contrast between Atralin and vehicle. It notes that the primary outcome has several categories or time points and is not reduced to one comparison. Without a defined contrast and its estimate, the endpoint description explains what was intended to be assessed, not whether the groups differed or how precisely any difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a randomized, triple-masked, parallel-group design. In general, random assignment is used to reduce systematic differences between groups at the start of a trial. Masking can reduce the influence of knowing the assigned treatment on behavior, clinical care, or measurement. A parallel design compares groups that receive different interventions over the study period. These are general explanations of the design terms; the registry record does not describe the detailed allocation procedure, the people masked, or how masking was maintained.

What can a participant count show?

The primary outcome is recorded as a number of participants, and the analysis type is described as binary. In general, a binary outcome places each participant into one of two states for a given analysis, such as meeting or not meeting a defined criterion. The count can then be compared across treatment groups. The meaning of such a comparison depends on the exact criterion, the assessment time, and the set of participants included. The registry record does not specify the threshold or category rule for this primary endpoint, and it does not report a single comparison of the categories or time points.

For count-based outcomes, the denominators matter as much as the event counts. A count without the number of participants assessed may not convey how complete the outcome data are. The primary endpoint population is described with LOCF and Complete-Case ITT labels, but group-specific analysis denominators and participant flow are not reported in the registry record. The adverse-event entries do state participants at risk, which allows the counts to be read in the context of those recorded denominators.

How should uncertainty be understood?

In general, an effect estimate describes the size and direction of a comparison, while a confidence interval communicates the estimate's statistical uncertainty. A narrow interval is more precise than a wide interval, under the assumptions used to construct it. A p-value addresses compatibility with a null hypothesis, but does not measure clinical importance or the probability that a treatment works. No single primary-outcome effect estimate, confidence interval, or p-value is reported in the registry record, so those concepts cannot be applied to a primary contrast for this trial.

For a binary outcome, common analyses may compare participant proportions or use a model for binary responses. Such analyses can depend on how the outcome is defined and whether the model adjusts for other variables. This is general statistical context, not a description of the analysis used in this trial. The registry record does not specify a model, covariate adjustment, confidence-interval method, or test for the primary comparison.

What does multiplicity mean?

Multiplicity arises when several hypotheses or outcomes are assessed. In general, testing many contrasts without an appropriate plan can make false-positive findings more likely across the collection of tests. A statistical analysis plan can identify the primary hypothesis, specify how secondary analyses will be interpreted, and set out any adjustment or hierarchical testing approach. The registry lists 26 outcome measures and 82 analyses, but does not report a complete testing hierarchy or state whether multiplicity was addressed. The number of entries alone does not establish that all were formal hypothesis tests.

The trial's outcome list includes quality of life, photodamage, ocular manifestations, phymatous changes, papulopustular signs, molecular markers of inflammation, molecular evidence of photodamage, and non-transient erythema. These outcomes cover different types of information and may require different measurement and analysis methods. The record does not provide enough detail to determine which analyses were confirmatory and which were exploratory.

What do the planning assumptions mean?

The registry's stated sample-size assumptions describe a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The target effect is described as a stated fraction of the observed effect. In general, a planning calculation estimates how many participants might be needed under specified assumptions; changing the effect size or other assumptions changes the resulting requirement. Such calculations are not observed power and do not show whether a trial was adequately planned or whether the observed result is persuasive.

The record does not report a protocol-based sample-size justification, nor does it provide enough detail to evaluate the assumptions used for a particular planned contrast. The enrollment was 68, but enrollment alone does not establish the number analyzed for the primary endpoint or the precision of an effect estimate. No conclusion about statistical power or adequacy of enrollment can be drawn from enrollment alone.

How do missing-data methods affect interpretation?

LOCF generally means that a participant's last recorded measurement is carried forward to a later assessment when a subsequent measurement is missing. This approach makes assumptions about how the outcome would have behaved after the last observation; those assumptions may not hold in every setting. Complete-case analyses generally use participants with observed data for the analysis in question. If missingness is related to outcomes or treatment, excluding incomplete records can affect the comparison. These are general descriptions rather than claims about the exact implementation in this trial.

The primary outcome population is labeled both LOCF and Complete-Case ITT in the registry record. The record does not describe how these labels relate to separate analyses, how missing values were handled at each time point, or how many participants had incomplete data. Without those details, readers cannot assess the extent or potential influence of missing outcome information.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 26 outcome measures and 82 analyses. These entries make multiplicity and selective interpretation relevant considerations, but the counts alone do not reveal how many distinct hypotheses were tested or which analyses were prespecified. The record does not report a complete statistical analysis plan, an ordering of primary and secondary hypotheses, or whether any adjustment for multiple comparisons was used.

In general, examining many outcomes or contrasts increases the chance that some results may appear notable by chance. Prespecifying a primary contrast and distinguishing it from supportive or exploratory analyses helps readers interpret the overall evidence. When a testing strategy is not reported, isolated findings among many analyses should be interpreted cautiously. No single primary-outcome comparison is available in the registry record, so it is not possible to assess the trial's principal contrast or its multiplicity strategy from a result estimate.

The primary outcome population is described with LOCF and Complete-Case ITT labels. These labels indicate that missing-data handling and analysis population were considered, but details are not reported: the record does not give numbers included in each analysis, reasons for missing assessments, or the exact implementation of LOCF and complete-case analyses. In general, LOCF carries an earlier observation forward, whereas a complete-case analysis uses records with the required observations. Both approaches depend on assumptions about incomplete data, and neither label alone tells readers whether those assumptions were reasonable in this trial.

The registry does not report participant flow by arm for the primary outcome, the number assessed at 24 weeks, or sensitivity analyses for missing data. It also does not explain whether the stated populations were used for separate analyses or how their results were reconciled. These omissions prevent a detailed assessment of attrition, missingness, and the robustness of the primary-outcome analysis.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: right hip osteoarthritis (2.2%).

The registry records serious adverse events for 0 participants among 22 at risk in the vehicle gel group and 1 participant among 46 at risk in the Atralin gel group. Other adverse events are recorded for 13 participants among 22 at risk in the vehicle group and 25 participants among 46 at risk in the Atralin group. These are participant counts with events, as indicated by the registry's outcome description; they are not a comparative statistical analysis.

Counts should be read alongside their recorded denominators. They do not show whether events were judged related to the assigned gel, how severe the non-serious events were, when they occurred, or whether participants stopped treatment because of them. Those details are not reported in the registry record. The record lists Right Hip Osteoarthritis at 2.2% among the leading serious adverse-event terms, but does not establish from that entry which group it occurred in or whether it was considered treatment-related.

Deaths are not reported in the registry record. A difference in raw counts, without an adjusted comparison and uncertainty estimate, should not be treated as evidence of a causal safety difference. These entries describe the reported events and denominators, not a complete assessment of safety.

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

The record establishes that a randomized, triple-masked, parallel-group phase 3 trial compared Atralin gel with vehicle gel in a study concerning ETR. It specifies a primary endpoint related to the severity of ETR signs, with a 24-week timeframe, and identifies several secondary outcome areas. It also records adverse-event counts and marks the study as terminated.

Those details do not establish whether Atralin changed the primary endpoint relative to vehicle. The registry does not report a single primary-outcome contrast, its uncertainty, or a p-value. The outcome description includes several signs, and the record indicates that there are multiple categories or time points rather than a single summarized comparison. Without the endpoint definition and a group comparison, neither the size nor direction of any primary effect can be determined from this record.

The trial summary explains why the investigators were interested in tretinoin, including a proposed relationship between photodamage and ETR. That rationale is not evidence that the intervention changed rosacea signs. Likewise, the fact that the trial was randomized and masked describes design features; it does not replace outcome results or resolve missing information about participant flow, adherence, or analysis methods.

The adverse-event counts provide descriptive safety information for the participants recorded at risk, but they do not demonstrate causation or provide a formal comparison. The listed serious adverse-event term also cannot be assigned to a treatment group from the information recorded. The terminated status is an additional limitation on interpretation because the reason and consequences of termination are not reported.

In general, conclusions about a treatment comparison depend on a clearly defined outcome, a suitable analysis, and an estimate with its uncertainty. Those elements are not available for a single primary comparison in the registry record. The appropriate reading is therefore limited: the record describes the trial design, planned outcomes, and some event counts, but does not provide the principal efficacy result needed to judge the primary comparison.

13. Why This Trial Matters Statistically

This trial illustrates why a registered endpoint and a reported result are different kinds of information. The registry identifies a primary outcome focused on ETR signs and gives its assessment timeframe, but the outcome description does not supply the scoring rule or a single comparison between groups. An endpoint title alone cannot show how much participants changed or how precisely the groups differed.

The record also demonstrates the importance of analysis populations. It names LOCF and Complete-Case ITT populations, but does not report the numbers analyzed or the detailed handling of missing assessments. A label can indicate an intended approach, but readers need participant counts and implementation details to judge how missingness may affect an estimate.

The listings of 26 outcome measures and 82 analyses underline the statistical importance of a clear analysis hierarchy. When a trial reports numerous outcomes, readers need to know which contrast addresses the main question, which analyses are secondary, and how multiplicity was considered. Those details are not reported in the registry record, and no single primary result is available to anchor interpretation.

Finally, the adverse-event entries show why counts need denominators and context. The registry gives participants at risk and participants with serious or other events, but does not provide causal assessments or a statistical comparison. Together, these features make the record useful for understanding the design and reporting gaps, while limiting what can be concluded about efficacy or comparative safety.

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 registry record does not provide a single primary-outcome comparison, an effect estimate, a confidence interval, or a p-value. It also notes that the primary outcome has several categories or time points and is not reduced to one comparison. This prevents assessment of the direction, magnitude, or statistical precision of the principal treatment contrast.

The endpoint description does not specify the scoring instrument, category thresholds, or the rule defining a participant count. Although redness is emphasized in the outcome title, the description also names telangiectasia, facial edema, and dry skin. The relationship between these signs and the recorded outcome categories is not reported.

Important details about participants and trial conduct are absent from the registry record, including detailed eligibility criteria, participant characteristics, treatment adherence, frequency changes, and group-specific participant flow. Enrollment was 68, but the number included in each primary-outcome analysis is not reported. The study is marked terminated, while the reason for termination and its effect on data collection or reporting are not reported.

The record lists LOCF and Complete-Case ITT populations but does not explain their implementation, give missing-data counts, or report sensitivity analyses. It also lists 26 outcome measures and 82 analyses without a complete analysis hierarchy or multiplicity strategy. The detailed protocol, statistical analysis plan, and rationale for the planned enrollment are not reported in the registry record.

Safety information is limited to event counts and denominators, with deaths not reported. The record does not provide event timing, relatedness, severity details for other adverse events, or a comparative analysis. These limitations restrict interpretation of both the primary outcome and the adverse-event entries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Atralin Gel for the Treatment of Rosacea — NCT01125930.
• Registry record last updated 2014-07-16; status last verified 2014-07.
• Results first posted 2014-07-16.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry record describes a randomized, triple-masked, parallel-group phase 3 trial of Atralin gel versus vehicle gel for a study concerning erythematotelangiectatic rosacea. Enrollment was 68. The study started in 2010-05, had a primary completion date of 2013-01, and is marked terminated. The reason for termination is not reported in the registry record.

The primary outcome concerns severity of ETR signs, including non-transient redness, with a 24-week timeframe. The registry identifies LOCF and Complete-Case ITT populations but does not report a single primary comparison. It lists 26 outcome measures and 82 analyses. Serious adverse events were recorded for 0 participants among 22 at risk in the vehicle group and 1 participant among 46 at risk in the Atralin group; other adverse events were recorded for 13 participants among 22 and 25 participants among 46, respectively.

The record describes the study question, design, outcomes, and some event counts, but does not report the principal primary-outcome estimate or its uncertainty.