Topical Dexamethasone and Tacrolimus for the Treatment of Oral Chronic Graft-Versus-Host Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Topical Dexamethasone and Tacrolimus for the Treatment of Oral Chronic Graft-Versus-Host Disease (NCT00686855), a randomized phase 2 study. The primary outcome is The Clinical Efficacy of Topical Steroid and Topical Tacrolimus Therapies for the Treatment of Oral cGHVD..

2. Clinical Question

The registry describes an open-label phase II randomized trial, NCT00686855, sponsored by Brigham and Women's Hospital. Participants completed a symptom survey at screening and again 4 weeks after starting therapy. Each symptom was scored from 0-10, with 0 representing none and 10 the worst. This approach focuses on how participants experienced their symptoms over the assessment period, rather than on an objective clinical measurement.

The primary question is framed around improvement in symptoms, but the registry does not report an efficacy comparison between the treatment groups. It also does not report the number of participants meeting the improvement threshold for each symptom or an estimate of the difference between treatments. The record therefore describes the intended comparison and outcome definition, but does not establish which treatment group had greater reported improvement.

3. Trial Design

NCT00686855 is recorded as a completed, randomized, open-label phase II trial with a parallel design. The treatments listed are topical dexamethasone and topical tacrolimus. Because masking was recorded as none, the trial was not blinded. The record does not describe how the random sequence was generated, how treatment assignments were concealed before enrollment, or whether any other allocation procedures were used.

The registry reports enrollment of 46 participants. Its primary outcome description says 36 were deemed evaluable for response. The reasons some enrolled participants were not included in the evaluable population are not reported in the registry record, nor are the group-specific numbers deemed evaluable. These details matter when interpreting a comparison: a randomized allocation does not by itself explain how participants who lack an evaluable outcome are handled in the analysis.

The stated assessment schedule was baseline and 4 weeks after therapy began. The arm description says the tacrolimus arm was closed to accrual as of January 2012; the record does not explain the circumstances or consequences of that closure. The study start is recorded as 2008-08, and primary completion as 2012-12. The record does not describe whether the closure changed the planned allocation or analysis.

The listed primary outcome concerns participants’ self-reported symptoms. Each symptom had a score, and a decrease of 3 points or further was defined as improvement. The registry lists one outcome measure but no analyses. Thus, the design and endpoint can be described, while the comparative efficacy result, analysis population, and methods used to account for missing observations cannot be reconstructed from 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: Of the 46 participants enrolled on the trial, 36 were deemed evaluable for response.

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 The Clinical Efficacy of Topical Steroid and Topical Tacrolimus Therapies for the Treatment of Oral cGHVD., measured over Participants were assessed at Baseline and 4 weeks after start of therapy.

The primary endpoint describes clinical efficacy through participants’ own ratings of oral sensitivity, mouth pain, and mouth dryness. A survey was administered at screening and again 4 weeks after the start of therapy. Each symptom score ranged from 0-10, where 0 meant none and 10 meant the worst. The registry defined improvement as a reduction of 3 points or further from pretreatment to post-treatment assessment.

Self-reported symptom measures are useful when the outcome of interest is how a participant experiences a condition. They can capture changes that may matter to participants even when the measurement is not an objective physical finding. The defined improvement threshold also gives a reader a rule for distinguishing a change considered an improvement from changes that do not meet that rule. This is a general explanation of patient-reported endpoints, not evidence that the threshold was validated for this trial.

The endpoint description does not specify how the three symptoms were combined, whether improvement was assessed separately for each symptom, or how participants with incomplete surveys were classified. The registry record does not report the numbers improving for each symptom, group-level results, or a statistical comparison. The outcome definition is available, but the observed endpoint results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting this trial requires separating the registered design, the endpoint definition, and the analysis results. The record describes randomized assignment to topical dexamethasone or topical tacrolimus, an open-label approach, and a parallel design. Randomization is generally intended to make treatment groups comparable in expectation, including with respect to factors that are measured and factors that are not measured. It does not guarantee that groups will be identical, and the registry does not report the sequence-generation or allocation-concealment procedures used in this trial.

What does open-label mean for interpretation?

Open-label means masking was recorded as none. Participants and clinical staff may therefore have known which treatment was being used. In general, knowledge of treatment can affect expectations, reporting, or assessment, especially when outcomes depend on subjective reports. This is a potential source of measurement influence, not evidence that reporting was biased in this trial. The registry gives no information about steps taken to limit such influence.

How should the symptom endpoint be understood?

The endpoint uses participant ratings of oral sensitivity, mouth pain, and mouth dryness. Each symptom score ranged from 0-10, and improvement was defined as a decrease of 3 points or further from pretreatment to post-treatment assessment. This definition turns a change in a score into an improvement classification. In general, a binary outcome can be reported as the number or proportion of participants meeting a prespecified classification in each group, followed by a comparison between groups. The registry does not report those counts or proportions, and it does not clarify whether each symptom was analyzed independently or combined into a single outcome.

Reducing a score change to an improvement classification can make a result easier to interpret, but it also discards information about the amount of change beyond the threshold. A participant whose score decreases by 3 points and one whose score decreases by more could both meet the definition. Conversely, a decrease that falls short of the threshold would not count as improvement under the stated rule. These are general properties of threshold-based outcomes, not observed patterns in this trial.

What would an effect estimate and confidence interval add?

In general, an effect estimate expresses the treatment-group contrast on a defined scale. For a binary outcome, possible scales include a difference in response proportions or a relative comparison of those proportions. The scale affects how the result is interpreted, so it should be stated alongside the estimate. No such estimate is reported in the registry record for this endpoint.

A confidence interval expresses the range of values compatible with the observed data under the analysis assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates more uncertainty. It is not a guarantee that the true effect lies within that range, and it does not by itself establish clinical importance. Because the registry reports no efficacy estimate or interval, the precision of the treatment comparison cannot be assessed.

What can a p-value establish?

In general, a p-value describes how unusual the observed data, or data more extreme, would be under a specified null hypothesis and statistical model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The registry lists no analyses and reports no p-value for the primary outcome. The two-sided significance level of 0.05 mentioned in the planning assumptions is not a reported efficacy result.

How should planning assumptions be read?

The registry describes planning illustrations using equal allocation between groups, a normal approximation, a two-sided significance level of 0.05, and an effect defined as a stated fraction of the observed effect. Such calculations are prospective illustrations of what a future design might require under chosen assumptions. They are not observed power and should not be treated as proof that the completed study could detect a particular effect. The registry does not report the trial's own sample-size justification, and no effect estimate from a reported primary analysis is available to evaluate against the planning assumptions.

For a binary outcome, the number of observed events and the number of participants contributing outcome data affect the information available to estimate a treatment contrast. A small number of events can make estimates unstable and intervals imprecise. This is a general statistical consideration; the registry does not provide the primary-outcome event counts needed to assess it for this trial.

Over-dispersion is a general concern for some count-data models when variability exceeds what the model assumes. It is not automatically relevant to a binary endpoint, and the registry does not report a model or analysis that would allow this issue to be evaluated. More broadly, the statistical method, covariate adjustment, missing-data approach, and handling of multiple symptom outcomes are not reported in the registry record. The absence of those details limits reproducibility and prevents an independent reconstruction of the primary comparison.

10. Multiplicity, Missing Data and Analysis Populations

The endpoint description names three symptoms: oral sensitivity, mouth pain, and mouth dryness. The registry also states that the primary outcome has several categories or time points and was not reduced to one comparison. It does not explain whether the symptoms were analyzed separately, how any combined outcome was defined, or which comparison was intended to carry the primary inference. When several outcomes or comparisons are assessed, the chance of a false-positive finding can increase if the analysis does not account for multiplicity. This is a general statistical concern; the record does not report a multiplicity strategy.

The registry reports 46 participants enrolled and 36 deemed evaluable for response. It does not report group-specific evaluable numbers, reasons for non-evaluability, missing survey counts, or the method used to handle missing endpoint data. It also does not state whether all randomized participants were included in the primary analysis. These omissions make it difficult to judge whether the reported evaluable population, if analyzed, would preserve the benefits of randomization.

The analysis population and analysis plan are not reported in the registry record. No imputation procedure, sensitivity analysis, interim analysis, or statistical analysis plan is described. These items should not be assumed to have been absent from the trial conduct; rather, they are not reported in the registry record. Because the record lists no analyses, it does not show how multiplicity or missing data affected the efficacy findings.

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 3.5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: squamous cell carcinoma (5.6%).

The registry lists serious adverse events for 0 of 28 participants in the dexamethasone group and 1 of 18 in the tacrolimus group. It lists other adverse events for 1 of 28 in the dexamethasone group and 1 of 18 in the tacrolimus group. These figures describe the posted counts and denominators. They do not, by themselves, establish that the treatments differ in safety.

The record lists “Squamous cell carcinoma” among the serious adverse-event terms, with 5.6% shown. The record does not connect that term to a specific treatment group in the available adverse-event details, so it should not be assigned to either group based on these figures alone. Death counts are not reported in the registry record; a blank or unreported count should not be read as evidence that no deaths occurred.

Adverse-event counts are most informative when their definitions, observation periods, severity criteria, and participant-level attribution are clear. Those details are not reported in the registry record. The figures should therefore be read as descriptive registry entries, not as a complete or adjusted comparison of safety.

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

The record establishes that NCT00686855 was a randomized, open-label phase II trial of topical dexamethasone and topical tacrolimus for oral chronic graft-versus-host disease. It also records the symptom survey, its assessment timing, the score range, and the rule used to define improvement. Those details make the intended clinical question understandable.

However, a defined outcome is not the same as a reported result. The registry does not give the number of participants who improved in either group, an estimate comparing the groups, a confidence interval, or a p-value. It is therefore not possible to determine from this record whether symptom reports favored either treatment or how precisely any observed difference was estimated. The absence of a reported efficacy analysis is not evidence that the treatments had equal outcomes.

The primary outcome relied on self-reported symptoms, which are meaningful for describing participants’ experiences but may be influenced by knowledge of treatment in an open-label study. This is a general interpretive consideration, not a finding that participants’ reports were biased. The record also does not explain why 36 enrolled participants were deemed evaluable for response or how missing outcome information was handled.

The adverse-event entries describe counts in the registry, but they do not provide a complete basis for comparing safety. They should not be used alone to infer a causal relationship, rule out risk, or determine whether one treatment is preferable. No medical recommendation follows from the posted information. The trial record is most informative about the question asked and the measurement plan; its efficacy and safety implications remain limited by the lack of reported comparative analyses and supporting detail.

13. Why This Trial Matters Statistically

This trial illustrates why a clear endpoint definition and a reported analysis are both necessary for statistical interpretation. The registry explains which symptoms participants rated, the scale used, when the ratings were collected, and what degree of reduction counted as improvement. That makes the intended measurement understandable. But without outcome counts or a treatment-effect estimate, readers cannot evaluate the comparison itself.

The difference between enrollment and evaluability is also important. The registry reports 46 enrolled participants and 36 deemed evaluable for response, without describing why some were not evaluable or how the analysis handled them. In general, the way missing or excluded observations are handled can affect how well a randomized comparison retains its intended interpretation. Reporting the analysis population and reasons for exclusions helps readers assess that issue.

The open-label design brings another useful statistical consideration into view: subjective endpoints can be affected by expectations or knowledge of treatment. This does not make self-reported outcomes invalid, nor does it demonstrate bias in this study. It does mean that interpretation benefits from transparent reporting of the analysis plan and safeguards, neither of which is detailed in the registry record.

Finally, planning calculations and observed results answer different questions. A planning illustration based on an assumed fraction of an observed effect is not observed power and cannot replace an estimate with an uncertainty interval. This record permits discussion of design and measurement, but not a statistically grounded conclusion about comparative efficacy.

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 interpreting efficacy is that the registry lists no analyses and does not report comparative outcome results. No group-specific symptom scores, improvement counts, effect estimates, confidence intervals, or p-values are reported. As a result, the direction, magnitude, and precision of any treatment difference cannot be assessed.

The endpoint description does not clarify whether oral sensitivity, mouth pain, and mouth dryness were treated as separate outcomes or combined. Although improvement is defined as a reduction of 3 points or further, the record does not explain how the threshold was applied across the symptoms or how participants with incomplete assessments were classified. This limits the ability to reproduce the endpoint from the registry description alone.

The registry reports 46 enrolled participants and 36 deemed evaluable for response, but does not give the reasons for non-evaluability or the number evaluable in each group. It does not describe an intention-to-treat analysis, a missing-data method, or sensitivity analyses. Those omissions prevent assessment of the impact of outcome availability on the randomized comparison.

The design was open-label, and the endpoint relied on participant reports. In general, knowledge of treatment can influence reporting or assessment; whether this occurred is not established by the record. Follow-up for the stated primary assessment was at baseline and 4 weeks after therapy began, so the registry does not provide evidence about symptom outcomes beyond that assessment. Allocation procedures, protocol details, and the trial's sample-size justification are also not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Topical Dexamethasone and Tacrolimus for the Treatment of Oral Chronic Graft-Versus-Host Disease — NCT00686855.
• Registry record last updated 2014-03-20; status last verified 2014-02.
• Results first posted 2014-02-19.
• 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.

18. Record Summary

NCT00686855 is recorded as a completed, randomized, open-label phase II trial with a parallel design, sponsored by Brigham and Women's Hospital. It enrolled 46 participants with oral chronic graft-versus-host disease and compared topical dexamethasone with topical tacrolimus. The tacrolimus arm description notes closure to accrual as of January 2012.

The primary outcome concerned self-reported oral sensitivity, mouth pain, and mouth dryness, assessed at baseline and 4 weeks after therapy began. Improvement was defined as a reduction of 3 points or further. The registry states that 36 participants were evaluable for response but lists no primary analyses. Comparative efficacy results and the reasons for non-evaluability are not reported in the registry record. Adverse-event counts are posted, but they do not constitute a complete comparative safety analysis.