Transdermal Patch to Monitor Inflammatory Biomarkers of GVHD: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Transdermal Patch to Monitor Inflammatory Biomarkers of GVHD (NCT02511782), a non-randomized na study. The primary outcome is CXCL10 in Skin.

2. Clinical Question

3. Trial Design

This completed study is listed as NCT02511782, with the title “Transdermal Patch to Monitor Inflammatory Biomarkers of GVHD.” Its official title describes noninvasive monitoring of inflammatory biomarkers of acute and chronic skin GVHD. The registry lists enrollment as 63, phase as NA, and allocation as non-randomized. Masking is listed as none, and the model is parallel. The sponsor is Children's Hospital Medical Center, Cincinnati. The study started in 2012-02, reached primary completion in 2014-06, and has completed status.

The registry describes three arms: acute GVHD, chronic GVHD, and healthy controls. The acute GVHD arm includes patients undergoing allogeneic hematopoietic cell transplantation at CCHMC who develop acute GVHD. Its description says the first baseline skin sample is obtained before the preparative regime. The chronic GVHD arm includes transplant recipients who develop chronic GVHD; skin samples are collected weekly for 4 weeks, with blood samples taken at the same time points. The healthy-control arm consists of healthy age-matched controls, potentially siblings of patients described in the record.

Because allocation is non-randomized and masking is absent, this design is observational rather than a randomized treatment comparison. The arms represent clinical groups rather than assigned interventions. Differences in measured biomarkers cannot, on their own, be attributed to GVHD without considering other differences between the groups. The registry describes a biomarker-monitoring objective, not a test of whether a therapy improves health outcomes.

The record does not report details such as the recruitment process, full eligibility criteria, or how many participants contributed samples to each analysis. The acute-arm description also notes that not all acute GVHD samples were analyzed for financial reasons. Enrollment therefore should not be read as the number of observations in the primary endpoint analysis.

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: We did not analyze all acute GVHD samples for financial reasons.

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 CXCL10 in Skin, measured over At time of GVHD diagnosis..

The primary endpoint is titled “CXCL10 in Skin.” It measures CXCL10 in skin, with the unit recorded as Skin CXCL10 femtograms/micrograms. The registry identifies the measure as a mean of a continuous variable, reports dispersion as the standard error, and sets the timeframe as the time of GVHD diagnosis. Skin CXCL10 was assessed using D-sqaume epidermal discs.

CXCL10 is being measured as an inflammatory biomarker: the study’s stated aim is to characterize local inflammatory responses and attempt to define biomarkers altered in acute or chronic skin GVHD. A skin-based measure is relevant to that aim because it samples the local tissue rather than relying only on a measurement from blood. The chronic-arm description also includes blood samples at the same time points as weekly skin sampling, but the primary endpoint listed in the registry is skin CXCL10.

In general, a group mean gives a summary of the measured values, while a standard error describes the precision of an estimated mean. It does not describe the full spread of individual participant values. The registry record does not report the primary endpoint’s numerical mean, standard error, analyzed sample size, or a comparison estimate. It also states that not all acute GVHD samples were analyzed for financial reasons. The extent and consequences of that omission are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary endpoint as a continuous measure summarized by its mean, with standard error as the dispersion measure. It does not report the numerical estimates or a detailed statistical analysis plan. The concepts below are general explanations of how these methods are usually interpreted, not claims about unreported procedures used in this study.

What does a mean summarize?

For a continuous measurement such as skin CXCL10, a mean represents the arithmetic average of the observed values in an analysis group. It gives a compact description of the group’s central level, but it can be influenced by unusually high or low observations. It also hides the distribution: two groups can have similar means but very different spreads or patterns of individual values. The record does not provide participant-level values or other distribution summaries, so the shape and spread of CXCL10 measurements cannot be assessed.

What does the standard error describe?

In general, a standard error quantifies the sampling uncertainty of an estimated mean. It is not the same as the standard deviation, which describes variation among individual observations. A standard error is useful for judging the precision of a mean, and it can contribute to constructing a confidence interval when the relevant method and assumptions are specified. The registry names standard error as the measure of dispersion but reports no numerical standard errors or confidence intervals for CXCL10.

A confidence interval, in general, gives a range of values compatible with the data under a specified statistical procedure. Its width reflects precision, while its position reflects the estimate. A confidence interval for a difference between groups is often more directly informative about the comparison than separate intervals for each group. No confidence interval or numerical group comparison for the primary endpoint is reported in the registry record.

Why does the design matter?

Random allocation can help balance both measured and unmeasured characteristics between treatment groups. This study is listed as non-randomized, and the arms describe clinical status rather than assigned treatments. That means measured differences between arms could be related to GVHD, but could also be related to other characteristics or circumstances. General statistical adjustment may address some measured differences, but it cannot automatically resolve unmeasured confounding. The record does not report an adjustment strategy.

Masking is listed as none. In general, knowledge of group status can affect decisions about measurement, sample handling, or interpretation, depending on how a study is conducted. The registry does not report whether any safeguards were used to limit such influences. The study uses skin sampling discs and describes sample collection procedures, but the record does not give enough detail to assess measurement reproducibility or laboratory blinding.

What can planning calculations say?

Any sample-size values associated with the posted results are planning illustrations based on an observed effect, not the trial’s own design justification. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. Such calculations describe hypothetical planning needs under those assumptions. They are not observed power, do not show that the study was adequately powered, and do not validate an observed effect. The registry record does not report the trial’s own sample-size justification.

Observed-effect planning can be particularly uncertain when the estimate comes from a small or selected dataset. Planning for a fraction of an observed effect is a scenario, not evidence that a future study will achieve that effect. The assumptions also do not resolve the non-randomized design, incomplete acute-sample analysis, or uncertainty about the endpoint analysis population. No numerical planning values are reported in the registry record.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model expects. If a model assumes less variation than the data contain, standard errors may be too small and tests may appear more certain than warranted. A continuous biomarker may show variability across participants or sampling conditions, but the record does not report a model, a variance assessment, or evidence of over-dispersion for CXCL10. This is a general consideration, not a finding about this study.

How should analyses be read?

Statistical interpretation depends on the outcome definition, analysis population, missing-data handling, model assumptions, and comparison being estimated. The registry identifies the endpoint and gives a brief note that some acute GVHD samples were not analyzed, but it does not report the analysis population, missing-data methods, inferential tests, or covariate handling. The record lists 2 outcome measures and 2 analyses, but does not say how those analyses relate to each other or whether any adjustment for multiple testing was applied. Without those details and numerical results, the strength and precision of a statistical conclusion cannot be assessed.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Acute Graft Versus Host Disease", "Healthy Controls", "Chronic Graft Versus Host Disease")
n   <- c(20, 10, 2)
m   <- c(273, 41, 7.5)
sp  <- c(95, 76, 2.11)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Acute Graft Versus Host Disease  20  273.000  424.853  74.163  471.837
CARM  Healthy Controls  10  41.000  240.333  -130.924  212.924
CARM  Chronic Graft Versus Host Disease  2  7.500  2.984  -19.310  34.310

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures and 2 analyses, and designates CXCL10 in skin as the primary endpoint. It does not describe whether the other measure or analysis was secondary, exploratory, or part of a prespecified testing sequence. No adjustment for multiple comparisons is reported in the registry record. In general, testing multiple outcomes or contrasts without accounting for multiplicity can increase the chance of a false-positive finding. The record does not provide enough information to determine how this issue was handled.

Missingness is directly relevant to the acute GVHD endpoint: the registry states that not all acute GVHD samples were analyzed for financial reasons. It does not report how many samples were excluded, the criteria used to choose samples for analysis, or whether exclusions were related to participant or measurement characteristics. It also does not describe imputation, sensitivity analyses, or other missing-data methods. Consequently, the representativeness of the analyzed acute samples cannot be assessed from the registry record.

The endpoint analysis population and the number of participants contributing to each group mean are not reported. Enrollment of 63 should not be interpreted as the endpoint sample size, particularly given the stated omission of acute samples. The registry does not explain the analysis population for the chronic GVHD or healthy-control arms, or whether samples were unavailable for other reasons. The effect of missing data on comparisons and precision is therefore unknown.

12. 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.

The registry reports serious and other adverse-event counts separately for the listed arms. For acute Graft Versus Host Disease, 0 serious events and 0 other events are recorded among 51 at risk for each category. For chronic Graft Versus Host Disease, 0 serious events and 0 other events are recorded among 2 at risk for each category. For Healthy Controls, 0 serious events and 0 other events are recorded among 10 at risk for each category.

These entries describe the registry’s reported counts; they do not establish that no adverse events occurred outside the reporting definitions, observation period, or submitted record. The registry’s death entries are null, so death counts are not reported in the registry record. No top serious-event terms are listed. The record does not provide additional detail about event collection, follow-up duration, or how adverse events were attributed. These safety entries should not be read as a comparative safety analysis or as evidence about treatment effects.

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

The registry record describes a study of local inflammatory biomarkers in people who develop acute or chronic skin GVHD after allogeneic hematopoietic cell transplantation, alongside healthy controls. Its primary measure is skin CXCL10 at the time of GVHD diagnosis. The record gives the endpoint definition and the general sampling approach, but does not report numerical results for CXCL10. It therefore does not establish whether measured levels differed among the clinical groups or how precisely any group estimates were determined.

The study’s aim is to attempt to define biomarkers that are altered in acute or chronic skin GVHD. A biomarker pattern in a study group would be an initial observation, not automatic evidence that the measure can reliably diagnose GVHD, monitor disease over time, predict outcomes, or guide care. The registry does not report diagnostic accuracy, validation in another population, or clinical-utility results.

The non-randomized design also limits causal interpretation. The clinical groups were not assigned at random, and the registry explicitly cautions that they are not a like-for-like control comparison. Any observed difference could reflect factors other than GVHD. Incomplete analysis of acute GVHD samples adds uncertainty about how well that group’s analyzed results would represent all relevant samples.

This record does not test a treatment’s effectiveness. D-SQUAME Skin Sampling Discs are used for sample collection, and the listed objective concerns measurement of biomarkers. The absence of numerical endpoint findings means the posted registry information cannot support a conclusion about the magnitude, precision, or clinical importance of CXCL10 differences. It also cannot establish that the sampling approach is sufficiently reproducible or informative for routine monitoring.

14. Why This Trial Matters Statistically

This study is statistically notable for asking whether local skin measurements can characterize inflammatory activity in acute and chronic GVHD, rather than relying only on a general clinical label or a blood-based measure. The endpoint is explicitly tied to skin CXCL10 and is measured at GVHD diagnosis. The chronic-arm description also pairs weekly skin sampling for 4 weeks with blood collection at the same time points, offering a longitudinal sampling framework in that arm.

At the same time, the design illustrates why a biomarker comparison requires more than a group mean. Non-randomized clinical groups may differ in ways that affect biomarker levels, and healthy controls are not necessarily an equivalent comparison group for transplant recipients with GVHD. The registry’s own caution that the arms are not a like-for-like control comparison is important when interpreting any group contrast.

Incomplete analysis of acute GVHD samples is another statistically consequential feature. The stated financial reason does not reveal whether the analyzed samples represent the broader group. Without the number and selection process for omitted samples, it is not possible to judge selection bias or the endpoint’s precision.

The registry record also shows the importance of transparent reporting. It identifies the primary endpoint and its measurement scale, but does not report the numerical endpoint results, analysis population, missing-data approach, or multiplicity procedures. Those omissions prevent readers from evaluating the size and uncertainty of any biomarker pattern. The study’s value as a biomarker investigation therefore depends on details that are not reported in the registry record, as well as on independent validation beyond an initial clinical-group comparison.

15. 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.

Several limitations specific to this study are apparent from the registry record. First, allocation is non-randomized, masking is listed as none, and the registry cautions that the arms are not a like-for-like control comparison. Differences between the GVHD groups and healthy controls therefore cannot be interpreted as caused by GVHD alone.

Second, the record says not all acute GVHD samples were analyzed for financial reasons. It does not report the number omitted, how analyzed samples were selected, or whether omitted samples differed from those retained. This creates uncertainty about the representativeness of the acute-group estimate.

Third, although CXCL10 in skin is identified as the primary endpoint, numerical results, endpoint analysis sample sizes, and comparison estimates are not reported in the registry record. The analysis population and missing-data procedures are also not reported. These gaps prevent assessment of both the size and precision of any result.

The registry describes the study at CCHMC and includes healthy age-matched controls, potentially siblings. The record does not report whether the findings were validated in other settings or populations. It also does not report detailed laboratory procedures, measurement reproducibility, covariate adjustment, or a statistical testing plan. These limitations are specific to the information available in the registry record and constrain interpretation of the biomarker objective.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Transdermal Patch to Monitor Inflammatory Biomarkers of GVHD — NCT02511782.
• Registry record last updated 2017-05-04; status last verified 2017-03.
• Results first posted 2017-05-04.
• 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.

19. Record Summary

NCT02511782 is a completed, non-randomized, unmasked parallel study sponsored by Children's Hospital Medical Center, Cincinnati. Enrollment is listed as 63; phase is NA. The study started in 2012-02 and reached primary completion in 2014-06. It concerns skin sampling with D-SQUAME Skin Sampling Discs in acute GVHD, chronic GVHD, and healthy-control groups.

The primary endpoint is mean skin CXCL10 at GVHD diagnosis, measured in Skin CXCL10 femtograms/micrograms, with standard error recorded as the dispersion measure. The registry states that not all acute GVHD samples were analyzed for financial reasons. Numerical primary endpoint results and analysis-population details are not reported in the registry record. Safety entries list zero serious and zero other affected events in each arm; death counts are not reported in the registry record.