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 Effectiveness of Topical Thalidomide to Treat Chronic Graft-Versus-Host-Disease Related Stomatitis (NCT00075023), a randomized phase 2 study. The primary outcome is Mean Percentage Change in Total Surface Area of Oral Ulceration..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00075023 |
| Phase | Phase 2 |
| Condition | Graft-versus-Host Disease, Stomatitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 10 |
| Arms in the primary outcome | 2 |
| Lead sponsor | National Institute of Nursing Research (NINR) |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with oral ulcerative stomatitis related to chronic graft-versus-host disease following allogeneic bone marrow or peripheral blood stem cell transplant. The registry record describes this intended population, but does not report the characteristics of the participants whose outcome data were posted.
Intervention
The intervention represented in the posted arms was thalidomide gel, 20 mg, applied topically 4 times daily for 4 weeks to a maximum of 3 target oral ulcers. This is distinct from taking thalidomide by mouth as a pill.
Comparator
The comparator was placebo gel with no thalidomide, applied topically 4 times daily for 4 weeks to a maximum of 3 target oral ulcers. The registry describes the placebo as an identical gel without thalidomide.
Primary question
The primary outcome asks how the total surface area of oral ulceration changed from baseline to 4 weeks, expressed as a mean percentage change. The posted means are -66.0 for thalidomide gel and -59.0 for placebo, with 3 participants in each arm. These arm-level summaries do not establish whether the groups differed statistically: a two-arm comparison is not reported in the registry record.
3. Trial Design
This was a Phase 2 randomized, triple-masked, parallel-group study. The registry lists thalidomide gel and placebo gel as its interventions. The posted outcome arms likewise compare those two topical treatments. The registry record gives enrollment as 10, while the primary outcome data are reported for 3 participants in each arm. The reason that these counts differ is not reported in the registry record.
The study summary describes a planned two-part design. The first part was a pilot of thalidomide gel applied to up to 3 oral ulcers. The summary says that, if the pilot were successful, a second part would test thalidomide mouthwash against placebo mouth rinse. However, the posted intervention arms and primary outcome results concern gel. Whether the mouthwash part began or was conducted is not reported in the registry record, so its planned description should not be read as evidence that it took place.
Participants in the gel comparison were described as using their assigned treatment 4 times daily for 4 weeks. The primary outcome timeframe was baseline to 4 weeks. Although the study is labeled triple-masked, the identities of the groups whose treatment assignment was masked are not reported in the registry record. Allocation concealment procedures, details of the randomization sequence, and the handling of treatment adherence are also not reported.
The record lists a start in 2003-12, primary completion in 2010-04, and status as terminated. It does not state why the study was terminated. Those administrative details do not, by themselves, establish whether the planned study was completed or why the posted outcome sample is limited.
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.
Pilot Study
| Stage | Thalidomide Gel | Placebo |
|---|---|---|
| STARTED | 5 | 5 |
| COMPLETED | 3 | 3 |
| NOT COMPLETED | 2 | 2 |
Reasons for not completing this period:
| Reason | Thalidomide Gel | Placebo |
|---|---|---|
| Physician Decision | 1 | 2 |
| Withdrawal by Subject | 1 | 0 |
Part Two
| Stage | Thalidomide Gel | Placebo |
|---|---|---|
| STARTED | 0 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 0 | 0 |
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.
Population: The sample size for the proof of concept study was calculated by using the data for aphthous ulcer percentage healing (personal communication with investigator) with topical thalidomide gel at 0 mg and 20 mg. This gave a total sample size of 60 using an alpha level = .05, beta = -.20 and a 2-tailed test. Assuming drop out rate of 10%, total is 66.
| Characteristic | Unit | Thalidomide Gel | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 5 | 5 | 10 | |
| Age, Customized: 27-60 yrs | participants | 5 | 5 | 10 |
| Sex: Female, Male: Female | Participants | NA | NA | NA |
| Sex: Female, Male: Male | Participants | NA | NA | NA |
| Region of Enrollment: United States | participants | 5 | 5 | 10 |
6. Primary Endpoint
The registry lists the primary outcome as Mean Percentage Change in Total Surface Area of Oral Ulceration., measured over baseline to 4 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | percentage change |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is mean percentage change in the total surface area of oral ulceration from baseline to 4 weeks. It describes change in the combined area of the ulcers being measured, rather than a change in ulcer count, pain, or a laboratory marker. The registry’s intervention descriptions refer to up to 3 target oral ulcers, but further details about how ulcer area was measured are not reported in the registry record.
A percentage change expresses the follow-up measurement relative to the baseline measurement, which can help describe change when participants begin with different ulcer areas. A negative value indicates a reduction in measured surface area over the timeframe; it does not, by itself, indicate whether a treatment caused that change. The placebo group is important because ulcer area could change over time for reasons not specific to the active gel. The relevant treatment question is whether changes differ between randomized groups, not whether either group’s mean is negative in isolation.
The registry identifies the endpoint as a mean and its dispersion as standard deviation, but does not post standard deviations or participant-level measurements. The posted means are -66.0 for thalidomide gel and -59.0 for placebo. With no reported dispersion or two-arm analysis, the precision of either mean and the uncertainty in the between-group contrast cannot be assessed from these summaries.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome gives mean percentage changes in total ulcer surface area of -66.0 in the thalidomide gel arm and -59.0 in the placebo arm, each based on 3 participants. Both means are negative, indicating that the reported group averages moved in the direction of reduced measured ulcer area from baseline to 4 weeks. These within-arm summaries do not answer whether the active gel produced a different change from placebo.
A treatment comparison depends on the contrast between arms and its uncertainty. The registry record does not report an analysis of that contrast. It also does not report a confidence interval, standard deviation, standard error, or participant-level outcome values. With such a small posted outcome sample, the means alone give limited information about how consistently individual participants changed. A group average can conceal variation among participants, and without a measure of spread it is not possible to judge that variation from the posted endpoint summaries.
The registry record lists one outcome measure and no posted analyses. It does not report a p-value or an adjusted estimate. No statistical significance claim can therefore be made from the outcome values alone. The record also does not report whether the endpoint was analyzed according to randomized assignment, whether participants with missing measurements were included, or whether any adjustments were planned or used.
The enrollment field lists 10 participants, while the primary outcome arms each list 3. The registry record does not explain the difference. It would be inappropriate to assume that participants without posted outcome values withdrew, were excluded for a particular reason, or had any particular outcome. The resulting uncertainty about who contributed to the endpoint limits interpretation of the arm summaries.
The safety record reports no serious adverse events among 5 participants at risk in either gel arm. It lists other adverse events affecting 2 of 5 participants in each arm. These are descriptive counts; they do not establish comparative safety, particularly with small denominators and no reported detail about event types in the posted serious-event terms. Death counts are not reported.
Overall, the registry provides a limited descriptive account of a small gel pilot comparison. It gives arm-level mean changes and adverse-event counts, but not the information needed to estimate the precision of the treatment contrast or to make a formal comparative inference. The terminated status and limited posted outcome sample are relevant context, while the reason for termination and the full disposition of participants are not reported in the registry record.
9. Statistical Methods Explained
A randomized parallel-group trial assigns participants to one of the treatment groups and follows the groups over the same general study period. Random assignment is intended to make treatment groups comparable on average, including for factors that may not have been measured. It does not ensure that small groups will be balanced in a particular trial. Here, the registry labels the design randomized and parallel, with thalidomide gel and placebo gel as the posted arms. The methods used to generate and conceal the allocation sequence are not reported in the registry record.
Masking is intended to reduce the influence of treatment knowledge on participant experience, care, measurement, or analysis. The record labels the study triple-masked. Which three roles were masked and how masking was maintained are not reported in the registry record. The label alone does not establish that masking was successful.
The primary endpoint is continuous: it is a mean percentage change in surface area. A mean summarizes the average value in a group, while a standard deviation describes how dispersed individual observations are around that average. The registry identifies standard deviation as the dispersion measure, but the posted arm summaries do not include those values. Without a measure of dispersion, the means cannot show how much participant-level outcomes varied.
A comparison of two means would ordinarily estimate how far apart the group averages are and quantify uncertainty around that estimate. A confidence interval is a range of values compatible with the data and the assumptions of the analysis; narrower intervals indicate greater precision, while wider intervals indicate less precision. The registry does not report a confidence interval, standard error, or analyzed two-arm contrast for this endpoint. As a result, the precision of the difference between thalidomide gel and placebo cannot be assessed from the posted results.
A p-value, when reported, describes how unusual data at least as incompatible with a specified null hypothesis would be under a statistical model. It is not a measure of the size or clinical importance of an effect. No p-value is reported for the endpoint, and the registry lists no posted analyses. It is therefore not possible to use the posted record to assess statistical significance. The absence of a reported analysis should not be replaced by an informal comparison of the two means.
Percentage change is a transformed outcome. A general consideration with percentage change is that participants with different baseline values may have different absolute changes even when their percentage changes are similar, and vice versa. The registry does not provide baseline ulcer areas or individual observations, so those features cannot be examined for this trial. Nor does it report the exact measurement procedures or whether any baseline adjustment was used.
The posted arm sizes for the primary endpoint are 3 participants per group, whereas the enrollment field lists 10. A denominator is essential for interpreting a mean and its precision. The posted endpoint values should therefore be understood as summaries for the listed outcome participants, rather than assumed to represent every enrolled participant. Reasons for the different counts, missing endpoint data, and rules for including participants are not reported in the registry record.
The record includes planning assumptions for illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation. Such illustrations address how many participants per arm might be needed under specified assumptions to detect a chosen fraction of an observed effect. They are not the trial’s reported design justification, and the registry does not report that these assumptions were used to plan the study. Because these illustrations use an observed effect, they are planning exercises rather than observed power. They do not supply the missing treatment comparison or resolve uncertainty in the posted estimates.
General statistical caution is especially important with small samples. A mean can be strongly influenced by individual observations, and the estimated spread may itself be uncertain. A null or absent significance test cannot be inferred from the size of the means, and a difference in the displayed means should not be treated as evidence of a reliable treatment effect. A meaningful comparative analysis would require an explicit between-group estimate and its uncertainty, together with clear information about which participants and measurements entered the analysis. Those details are not reported in the registry record.
For adverse events, counts and denominators describe how many participants were reported as affected among those at risk. They are not a substitute for event descriptions, timing, severity, or a formal comparison. In this record, serious adverse events are reported as zero affected in each arm, while other adverse events are reported separately. The small at-risk groups make these figures descriptive, and they cannot establish that an event is impossible or that the groups have equivalent safety profiles.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when several outcomes, time points, subgroups, or analyses are examined: repeated opportunities to find a notable result can complicate interpretation of isolated statistical findings. The registry lists one outcome measure and no posted analyses. It does not report a statistical plan describing a primary analysis, any adjustment for multiple testing, or whether additional unposted outcomes or analyses were considered. No multiplicity adjustment can be assumed.
Missing-data handling is not reported in the registry record. The enrollment field lists 10 participants, while the primary endpoint arms list 3 participants each. The record does not explain this difference, state how many participants had a baseline or 4-week measurement, or describe any imputation or sensitivity analysis. It is therefore not possible to determine whether the posted means represent all randomized participants or a subset with available measurements.
The analysis population is also not reported in the registry record. In particular, it does not say whether participants were analyzed according to randomized assignment, whether treatment use or adherence affected inclusion, or whether any participants were excluded after randomization. These choices can affect interpretation, especially when the number contributing to the endpoint is small.
The record’s statistical-analysis count is zero. This indicates that no analysis is posted in the registry record, not that no analysis was conducted elsewhere. Any unreported analysis methods, multiplicity procedures, missing-data assumptions, or analysis populations remain unknown and should not be inferred from the arm-level means.
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 |
|---|---|---|---|
| Thalidomide Gel | 0 | 5 | 0.0% |
| Placebo | 0 | 5 | 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 |
|---|---|
| Thalidomide Gel | 2 of 5 |
| Placebo | 2 of 5 |
| Adverse Events for All Participants | 6 of 10 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Thalidomide Gel | Placebo | Adverse Events for All Participants |
|---|---|---|---|---|
| Increase in oral pain | General disorders | 1 of 5 | 1 of 5 | 0 of 0 |
| thrush | General disorders | 0 of 0 | 0 of 0 | 2 of 10 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 0 of 0 | 0 of 0 | 2 of 10 |
| Oral pain | General disorders | 0 of 0 | 0 of 0 | 2 of 10 |
| Sore throat | General disorders | 0 of 0 | 0 of 0 | 2 of 10 |
| Spouse pregnancy | Social circumstances | 0 of 5 | 1 of 5 | 0 of 0 |
| Pneumonia | Respiratory, thoracic and mediastinal disorders | 1 of 5 | 0 of 5 | 0 of 0 |
| Dyspnea on exertion | Respiratory, thoracic and mediastinal disorders | 0 of 0 | 0 of 0 | 1 of 10 |
| headache | General disorders | 0 of 0 | 0 of 0 | 1 of 10 |
| tired | General disorders | 0 of 0 | 0 of 0 | 1 of 10 |
The serious adverse-event figures are reported separately by arm. In the thalidomide gel group, 0 of 5 participants at risk were reported as affected by a serious adverse event; in the placebo group, the corresponding count was 0 of 5. The registry also lists no serious adverse-event terms. These counts describe what was recorded in this trial and do not establish that serious events could not occur.
The denominator for these safety counts differs from the primary endpoint sample size, which is 3 participants per arm. The record does not explain the difference. It reports other adverse events affecting 2 of 5 participants in each arm, and 6 of 10 participants overall. Those figures should not be confused with the serious-event counts.
Deaths are not reported in the registry record. A missing death count should not be interpreted as a count of zero. The record does not provide further detail about the types, timing, severity, or relationship of other adverse events to treatment. With these small groups and limited event detail, the posted counts are descriptive and do not support a precise comparison of safety between treatments.
12. What the Result Does, and Does Not, Mean
The registry result establishes that the posted mean percentage change in total oral-ulcer surface area from baseline to 4 weeks was -66.0 for thalidomide gel and -59.0 for placebo gel. Each arm’s endpoint summary includes 3 participants. It is a description of the observed group averages, not a reported test of whether the treatments differ.
Because a two-arm analysis and measures of uncertainty are not reported, the record does not establish how precise either mean is or how compatible the observed data are with a range of possible between-group effects. The displayed arm means should not be used on their own to claim that thalidomide gel is better, worse, equivalent, or ineffective compared with placebo. A within-arm reduction is not the same as a treatment effect: changes can occur in both groups, and the comparative effect depends on the contrast between them.
The result also does not establish that the findings apply to all patients with chronic graft-versus-host-disease-related stomatitis. The endpoint counts are small, the registry does not describe the characteristics of those participants, and the gap between enrollment and endpoint counts is unexplained. The reason for the terminated status is not reported, so it cannot be attributed to the observed outcome, safety, recruitment, or any other cause.
The safety figures likewise have a limited meaning. No serious adverse events were reported among the listed participants at risk in either arm, while other adverse events were recorded in both groups. These counts do not rule out uncommon events or establish comparative safety. Death counts and further event details are not reported in the registry record.
In short, the posted data document small-sample arm summaries for a topical gel pilot comparison. They do not provide the inferential analysis, precision estimates, participant accounting, or broader context needed for a definitive treatment comparison. The registry record supports describing what was reported, but not drawing conclusions beyond those observations.
13. Why This Trial Matters Statistically
This trial illustrates why reporting arm-level means is not enough for a comparative interpretation. A randomized design is intended to support a comparison between assigned groups, but the key quantity is the between-group contrast and its uncertainty. The registry posts two means for a continuous endpoint, yet does not post the contrast, a confidence interval, or a statistical test. Readers should distinguish the presence of numerical outcome data from the availability of an interpretable comparative analysis.
The difference between the enrollment count and the endpoint counts is also statistically important. The record lists 10 enrolled participants but reports endpoint results for 3 participants in each arm. Without an account of participant flow and missing outcomes, it is difficult to assess how representative the posted summaries are of those randomized. This is not a basis for assuming a particular cause of missing data; it is a reason to recognize the uncertainty left by the record.
The adverse-event summaries provide a related lesson about denominators. Safety counts use 5 participants at risk per arm, unlike the primary endpoint summaries. Keeping those populations distinct avoids treating outcome and safety figures as though they necessarily describe the same participants. The absence of reported serious events is informative as a record of observed counts, but small denominators and limited event detail restrict what can be concluded.
Finally, the study summary describes a possible second, mouthwash part conditional on the pilot. The posted arms and endpoint results concern gel, and the record does not establish that the mouthwash part proceeded. Separating planned study aims from posted results is essential when interpreting a terminated, small pilot record. Together, these features make the trial a useful example of how design labels, outcome summaries, sample accounting, and analysis reporting each contribute different information.
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 primary outcome is reported only as a mean percentage change in each arm, with 3 participants per arm. Standard deviations are not posted despite being identified as the dispersion measure, and no participant-level values or confidence intervals are available. Consequently, neither variability within groups nor precision of the treatment contrast can be assessed.
The registry lists 10 participants enrolled but only 3 participants in each primary outcome arm. It does not explain the difference or report participant flow, missing measurements, exclusions, or the analysis population. The safety denominators are 5 participants per arm, so the outcome and safety summaries do not share the same listed denominators. The reason for this difference is not reported.
No statistical analysis is posted for the primary endpoint. The record does not report a formal comparison, a p-value, an adjustment method, or an analysis plan. It also does not describe the measurement procedure in detail, report baseline ulcer-area values, or explain how multiple ulcers contributed to the total surface-area outcome. These gaps limit assessment of how the endpoint was constructed and analyzed.
The registry describes a planned second study part involving mouthwash if the pilot were successful, but the posted intervention arms and results concern gel. Whether the second part occurred is not reported. The record is marked terminated, but the reason for termination is not reported. Neither the conditional plan nor the status label identifies why the study ended.
Safety reporting is limited to counts of affected participants, without further event descriptions in the posted serious-event terms. Deaths are not reported. These limitations mean that the safety counts should be read as a narrow account of reported events rather than a complete characterization of risk.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Effectiveness of Topical Thalidomide to Treat Chronic Graft-Versus-Host-Disease Related Stomatitis — NCT00075023.
- Registry record last updated 2015-11-04; status last verified 2015-10.
- Results first posted 2015-11-04.
- 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
The registry record describes a Phase 2 randomized, triple-masked, parallel-group comparison of topical thalidomide gel and placebo gel for chronic graft-versus-host-disease-related oral ulceration. The planned gel regimen was 4 times daily for 4 weeks, applied to a maximum of 3 target ulcers. The primary endpoint was mean percentage change in total ulcer surface area from baseline to 4 weeks.
The posted endpoint means were -66.0 for thalidomide gel and -59.0 for placebo, with 3 participants in each arm. No two-arm analysis or measures of uncertainty are reported. The enrollment field lists 10 participants; the reason for the difference from the endpoint counts is not reported. Safety counts list zero serious adverse events among 5 participants at risk in each arm and other adverse events affecting 2 of 5 in each arm. Death counts are not reported.
The record is marked terminated, with primary completion in 2010-04. The reason for termination and whether the conditional mouthwash part proceeded are not reported in the registry record.