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 Study of Etanercept for the Prevention of Complications Resulting From Hematopoietic Stem Cell Transplantation (HSCT) (NCT00141739), a na phase 2 study. The primary outcome is The Percentage of Participants Experiencing Acute GVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00141739 |
| Phase | Phase 2 |
| Condition | Graft-Versus-Host Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 100 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Michigan Rogel Cancer Center |
| Results posted | Yes |
2. Clinical Question
Population
Patients undergoing a full intensity allogeneic hematopoietic stem cell transplant. The registry record lists 100 participants enrolled and identifies graft-versus-host disease as the condition under study.
Intervention
Etanercept given prophylactically in addition to standard GVHD prevention medicines. The listed study arm is GVHD prophylaxis with etanercept.
Comparator
No concurrent comparator arm is listed. The trial is described as single group, and allocation is listed as NA.
Primary question
What percentage of participants experienced acute GVHD within 100 days after transplantation while receiving etanercept with standard prophylaxis? The outcome description says incidence of grades 2-4 and grades 3-4 GVHD was calculated. The corresponding results are not reported in the registry record.
The study summary also frames the intervention around two concerns: reducing acute GVHD and reducing the risk of death. However, the listed primary outcome is the percentage of participants experiencing acute GVHD, and the registry record does not report a mortality result. This distinction matters because a study question may mention several goals while the posted outcome list and result fields describe a narrower set of measured endpoints.
With one study group and no listed comparison group, the record can describe events among participants who received the regimen. It cannot, by itself, establish how those event rates compare with outcomes under standard prophylaxis alone. The clinical question is therefore descriptive in the posted results, rather than a direct randomized comparison of adding etanercept versus not adding it.
3. Trial Design
This is a phase 2, single-group intervention study. The registry record lists etanercept as the drug intervention and describes the arm as GVHD prophylaxis with etanercept. The official title specifies patients undergoing a full intensity allogeneic hematopoietic stem cell transplant. The study summary describes etanercept as an addition to standard preventative medicines.
The record lists 100 participants enrolled. Allocation is listed as NA, the study model as single group, and masking as none. These details mean that the posted design does not include a randomized allocation between the etanercept regimen and a separate control regimen. There is consequently no contemporaneous control arm in the registry record against which the observed event frequency can be directly compared.
The study is marked completed. The listed start is 2004-08 and the primary completion is 2011-08. These dates describe the registry record; they do not provide information about the timing of individual participant follow-up or when outcome data were analyzed.
Five outcome measures and one analysis are listed. The primary outcome concerns acute GVHD after transplantation, with a timeframe of 100 days. Secondary outcomes concern etanercept toxicity, idiopathic pulmonary syndrome, a TNFR1 ratio in TBI-treated versus non-TBI-treated patients, and the impact of TNF polymorphisms on response to therapy. The detailed methods for these outcomes, including analysis populations and missing-data handling, are not reported in the registry record.
The registry record does not report the sample-size justification or a prespecified statistical analysis plan. A planning illustration based on the observed effect is not the trial's original design justification. It should be read as a hypothetical planning exercise, not as evidence about how the trial was designed or whether it had adequate power for its original aims.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Patients \>1 year of age who were candidates for a myeloablative allo-hemopoietic cell transplant were eligible for inclusion. Donors and recipients were required to match for 7/8 or 8/8 HLA-A, HLA-B, HLA-C, and HLA-DRB1 loci. Patients with an 8/8 HLA-matched related donor were not eligible.
Overall Study
| Stage | GVHD Prophylaxis |
|---|---|
| STARTED | 100 |
| COMPLETED | 100 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: To provide Sufficient power
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | GVHD Prophylaxis |
|---|---|---|
| Participants analysed | 100 | |
| Age, Continuous | years | 47 (full range 5) |
| Gender: Female | Participants | 43 |
| Gender: Male | Participants | 57 |
| Region of Enrollment: United States | participants | 100 |
| Disease status at transplantation: Low risk | participants | 39 |
| Disease status at transplantation: Intermediate risk | participants | 33 |
| Disease status at transplantation: High risk | participants | 28 |
| Donor match: 8/8 matched unrelated | participants | 71 |
| Donor match: 7/8 mismatched unrelated | participants | 26 |
| Donor match: 7/8 mismatched related | participants | 3 |
| Conditioning Regimen Parameter: Non-Total body radiation | participants | 71 |
| Conditioning Regimen Parameter: Total body radiation | participants | 29 |
6. Primary Endpoint
The registry lists the primary outcome as The Percentage of Participants Experiencing Acute GVHD After Allogeneic Hematopoietic Stem Cell Transplantation (HSCT), measured over 100 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the percentage of participants experiencing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation, with a stated timeframe of 100 days. The outcome description says incidence was calculated for grades 2-4 and grades 3-4 GVHD. It also describes a clinical grading system from 0 to IV, with grades characterized by the extent of skin, liver, or gastrointestinal involvement.
A percentage endpoint expresses how common an event was among the participants assessed. For a binary outcome such as whether a participant experienced GVHD, each participant contributes an event or a non-event under the applicable outcome definition. The denominator and rules for determining which participants are assessed are important for interpreting that percentage. The analysis population and missing-data rules are not reported in the registry record.
Acute GVHD is the direct event named in the primary outcome, and the 100-day timeframe defines the period of interest. The endpoint description also mentions an aim to determine whether the regimen would decrease 100-day mortality, but mortality is not the primary outcome title. No mortality result is reported in the registry record. The registry record also does not report the numerical results for either stated GVHD grade range, so the incidence and its precision cannot be assessed from the posted results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies acute GVHD incidence within 100 days as the primary outcome, with grades 2-4 and grades 3-4 described as the categories of interest. It does not report the numerical result for either category. As a result, the posted record does not establish the observed percentage of participants experiencing acute GVHD, nor does it show how precise an estimate might be. The record's stated enrollment of 100 does not substitute for an endpoint denominator, since the number included in each analysis and the handling of missing outcome information are not reported.
The study design also limits what can be inferred from any event rate in this group. A single-group result can describe outcomes among people receiving etanercept with standard prophylaxis. Without a concurrent comparison group, it cannot isolate the contribution of etanercept from the effects of standard prophylaxis, transplantation, participant characteristics, or other care. The record therefore does not support a direct estimate of the treatment contrast that would answer what would have happened to comparable participants without etanercept.
The study summary mentions reducing the risk of death as well as acute GVHD. The primary outcome field is focused on GVHD incidence, and the deaths field in the safety data is null. A mortality endpoint result is not reported in the registry record. A null field should not be interpreted as zero deaths; it means the record does not give a count there.
Safety data list 25 participants affected among 100 at risk in the serious adverse event category and 89 among 100 at risk in the other adverse event category. These are descriptive registry figures. They do not establish that the events were caused by etanercept, and the record does not state whether the categories overlap. Serious adverse event terms listed include Diarrhea and Infection without Neutropenia, each at 6.0%, and Hypoxia at 4.0%. These term percentages should not be treated as the primary endpoint or as a comparison against another regimen.
Statistical precision is also not available for the primary result because its numerical estimate and confidence interval are not reported. A confidence interval, in general, describes uncertainty around an estimated quantity under the assumptions of the analysis. Without the estimate, interval, denominator, and analysis method, readers cannot evaluate whether the primary outcome estimate is narrow or wide. No p-value or adjusted effect estimate is reported in the registry record.
Overall, the record documents the design and lists selected outcome and safety information, but it does not provide the primary GVHD result needed to quantify the outcome. The single-group design would remain an important limitation even if a numerical event percentage were available, because observed events in this group alone would not show the effect of adding etanercept relative to a separate regimen.
9. Statistical Methods Explained
The primary outcome is a binary event summarized as a percentage of participants. The outcome description identifies acute GVHD after transplantation and gives a 100-day timeframe. It says that incidence for grades 2-4 and grades 3-4 was calculated. The statistical method used to produce those results is not reported in the registry record, and the numerical endpoint results themselves are not reported there.
What does a percentage measure?
In general, a percentage for a binary endpoint is based on the number of participants meeting the event definition relative to the number assessed under that outcome. It is important to know both quantities and how the analysis population was formed. For example, a stated enrollment total may differ from the number whose outcome status is available. The registry record lists enrollment of 100, but does not report the denominator used for the primary analysis or how participants with unavailable outcome information were handled.
The event definition also matters. The record names grade ranges and gives descriptions of grades 0 through IV, including combinations of skin, liver, and gastrointestinal involvement. An analysis of grades 2-4 and one of grades 3-4 do not represent the same event threshold. The record does not provide the outcome counts or clarify the detailed adjudication and assessment procedures, so the numerical incidence cannot be reconstructed from the description alone.
Why does the study design affect interpretation?
This is a single-group study with no listed comparator. In general, a single-group estimate describes outcomes under the observed care regimen; it does not provide the counterfactual outcome that the same participants would have experienced under another regimen. Consequently, a difference attributable to adding etanercept cannot be estimated from a direct between-group comparison in this record. The absence of random allocation also means the record does not describe a randomized comparison.
This is distinct from the question of whether a percentage is calculated correctly. A well-defined descriptive estimate can still lack a causal comparator. Conversely, even a comparison would require information about outcome definitions, analysis populations, and statistical methods to judge how it was made. The registry record does not report a detailed analysis plan, adjusted model, or inferential procedure for the primary endpoint.
What would precision information add?
In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical procedure and its assumptions. Its width communicates precision: a wider interval indicates more uncertainty than a narrower interval. It does not by itself resolve design limitations or prove that a treatment caused an outcome. No primary endpoint confidence interval is reported in the registry record. The outcome estimate and analysis denominator are also not reported, so precision cannot be evaluated from the listed primary outcome description.
The endpoint is a proportion, so methods for proportions would ordinarily need to account for the observed event count and the analysis denominator. The registry record does not identify which interval or test method, if any, was used. It would be inappropriate to assume a particular method or derive a new interval from enrollment alone.
How should planning illustrations be read?
The planning illustration assumptions state a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They also state that the effect to detect is a specified fraction of the observed effect. For outcomes other than time-to-event outcomes, the illustration is expressed as participants per arm. These are assumptions for a planning exercise based on the observed effect, not reported features of the trial's original design. The registry record does not report the original sample-size justification.
Such planning quantities are hypothetical: they address what sample size might be needed under stated assumptions for a future comparison. They are not observed power, and they do not change the single-group design of this study. The record does not list the resulting planning quantities in the registry record for this explanation, so no numeric sample-size result can be stated.
Why is over-dispersion relevant in general?
For outcomes that are counts, over-dispersion means that variability is greater than a simple model would expect. In general, ignoring excess variability can make standard errors too small and intervals too narrow. That concept does not define the primary endpoint here, which is described as a percentage of participants with an event. No count model or over-dispersion adjustment is reported for this trial, so it should not be assumed to have been used.
In short, the registry record supplies an outcome definition and design description but not the primary outcome estimate, precision measure, analysis population, or detailed statistical method. General statistical principles explain what those missing details would contribute, but cannot replace them.
10. Multiplicity, Missing Data and Analysis Populations
The record lists five outcome measures, including the primary acute GVHD outcome and secondary measures concerning etanercept toxicity, idiopathic pulmonary syndrome, TNFR1 ratio by TBI status, and TNF polymorphisms. It lists one analysis. These registry entries do not explain whether or how multiple outcomes or subgroup comparisons were handled in the statistical analysis.
When several endpoints or comparisons are examined, the chance of at least one apparently notable result can increase. In general, a prespecified multiplicity strategy can clarify which results are confirmatory and how inference is adjusted. The registry record does not report a multiplicity plan, a hierarchy among outcomes, or any adjustment procedure. It is therefore not possible to determine from this record how multiple testing was considered.
Missing-data handling is not reported in the registry record. The stated enrollment is 100, but the primary analysis denominator, the number with assessable GVHD status, and any rules for incomplete follow-up are not given. The analysis population is also not reported. These details matter because excluding participants with unknown outcomes or using another approach can affect the percentage and its interpretation.
The record does not describe an intention-to-treat analysis, a per-protocol analysis, or a method for imputing missing outcomes. No assumption about those choices should be inferred from the listed enrollment or study completion status. Since the primary result is itself not reported, the impact of missing information on the endpoint cannot be evaluated.
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 |
|---|---|---|---|
| GVHD Prophylaxis | 25 | 100 | 25.0% |
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 |
|---|---|
| GVHD Prophylaxis | 89 of 100 |
Most frequent serious adverse event terms
| Event term | Organ system | GVHD Prophylaxis |
|---|---|---|
| Diarrhea | Gastrointestinal disorders | 6 of 100 |
| Infection without Neutropenia | Infections and infestations | 6 of 100 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 4 of 100 |
| Hyperglycemia | Metabolism and nutrition disorders | 3 of 100 |
| Hypotension | Vascular disorders | 3 of 100 |
| Blood Bone Marrow - Other | Blood and lymphatic system disorders | 2 of 100 |
| Depressed Level of Consciousness | Nervous system disorders | 2 of 100 |
| Hypocalcemia | Metabolism and nutrition disorders | 2 of 100 |
| Syncope | Nervous system disorders | 2 of 100 |
| Adult Respiratory Distress Syndrome (ARDS) | Respiratory, thoracic and mediastinal disorders | 1 of 100 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GVHD Prophylaxis |
|---|---|---|
| Hyperglycemia | Metabolism and nutrition disorders | 30 of 100 |
| Hypoxia | Respiratory, thoracic and mediastinal disorders | 30 of 100 |
| Anorexia | Metabolism and nutrition disorders | 24 of 100 |
| Febrile Neutropenia | Blood and lymphatic system disorders | 24 of 100 |
| Hypertension | Vascular disorders | 24 of 100 |
| Hypotension | Vascular disorders | 22 of 100 |
| Hypokalemia | Metabolism and nutrition disorders | 18 of 100 |
| Stomatitis Pharyngitis | Infections and infestations | 18 of 100 |
| Dyspnea | Respiratory, thoracic and mediastinal disorders | 16 of 100 |
| Hypocalcemia | Metabolism and nutrition disorders | 15 of 100 |
Serious events with the highest arm-level rate: diarrhea (6.0%), infection without neutropenia (6.0%), hypoxia (4.0%), hyperglycemia (3.0%), hypotension (3.0%).
The registry safety data list 100 participants at risk in the GVHD prophylaxis group. In the serious adverse event category, 25 are listed as affected; in the other adverse event category, 89 are listed as affected. These figures describe the registry's reported participant counts in each category. The record does not say whether a participant could appear in both categories, so the counts should not be added together.
The listed serious adverse event terms include Diarrhea at 6.0%, Infection without Neutropenia at 6.0%, Hypoxia at 4.0%, Hyperglycemia at 3.0%, Hypotension at 3.0%, and Blood Bone Marrow - Other at 2.0%. They are reported as percentages, not as a complete account of every event or every participant's experience. The record does not report severity details beyond the serious adverse event categorization, nor does it state that these events were caused by etanercept.
The deaths field is null. It is therefore not a reported count and should not be read as zero. These safety entries are descriptive for a single-group study; no control-group safety comparison is listed.
12. What the Result Does, and Does Not, Mean
The posted record establishes that a phase 2, single-group study evaluated etanercept added to standard GVHD prophylaxis in the setting of allogeneic hematopoietic stem cell transplantation. It identifies acute GVHD within 100 days as the primary outcome and describes incidence for grades 2-4 and grades 3-4. It also lists selected safety outcomes and other secondary outcomes.
The primary endpoint result is not reported in the registry record. Therefore, readers cannot use this record to state what percentage experienced acute GVHD, how precise that estimate was, or whether the event rate met a particular target. The summary's mention of a goal related to mortality does not supply a mortality result; the deaths field is null, and no mortality estimate is reported.
Even if a single-group event rate were available, it would describe participants receiving the regimen rather than estimate the effect of etanercept relative to a concurrent control. The record lists no comparator arm and no random allocation. Differences between outcomes under this regimen and outcomes from another setting cannot be attributed to etanercept on the basis of this record alone.
The safety figures show reported adverse event counts and selected serious-event term percentages for the study group. They do not establish causation, comparative risk, or the complete safety profile. The registry record does not provide the clinical detail or analysis needed to draw those conclusions.
Accordingly, the record is informative about the intervention, study structure, endpoint definition, and some safety reporting. It is not sufficient to quantify the primary outcome or to determine comparative effectiveness. Those distinctions separate what the registry documents from what would require a reported endpoint estimate, its precision, and a suitable comparison design.
13. Why This Trial Matters Statistically
This trial is statistically notable because its central clinical question concerns the addition of etanercept, while the listed design is single group. A single-group study can document event frequencies under the regimen used, but it lacks the concurrent control needed for a direct estimate of the effect of adding the drug. Recognizing that distinction prevents descriptive outcomes from being read as treatment contrasts.
The primary outcome definition also illustrates why endpoint details matter. The record identifies a 100-day period and two GVHD grade ranges, but does not report the corresponding estimates or analysis denominators. Without those pieces, even a clearly named clinical outcome cannot be evaluated for frequency or precision. A definition is not a result.
The record also distinguishes between a study's stated aims and its posted outcome results. The summary mentions both acute GVHD and death, but the listed primary endpoint is acute GVHD and the deaths field is null. Statistical interpretation depends on the outcome and result actually reported, not only the rationale described in a study summary.
Finally, planning illustrations based on an observed effect are not substitutes for an original sample-size justification or a prospective comparison. The stated assumptions describe hypothetical planning, while the actual trial has no listed comparison arm. Keeping those roles separate helps readers understand what the study can describe and what it cannot establish.
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 has important reporting limitations for interpretation. It does not report the numerical result for the primary acute GVHD outcome, despite identifying the outcome and its 100-day timeframe. It also does not report the primary analysis denominator, a confidence interval, or a p-value. The incidence of grades 2-4 and grades 3-4 GVHD therefore cannot be quantified from the record.
The single-group design and absence of a listed comparator limit causal interpretation. Allocation is listed as NA and masking as none. The record does not provide a randomized contrast against standard prophylaxis without etanercept, so it cannot directly estimate the added effect of etanercept.
The registry record does not report the original sample-size justification, detailed statistical analysis plan, multiplicity approach, missing-data rules, or analysis populations. It does not explain how participants with incomplete outcome information were treated. The planning illustration assumptions are not the trial's prospective design justification.
The summary refers to mortality as an aim, but a mortality result is not reported. The deaths field is null. The listed safety data also lack a concurrent comparison group and do not establish whether reported events were attributable to the intervention. These limitations are specific to the information and design described in the registry record.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Etanercept for the Prevention of Complications Resulting From Hematopoietic Stem Cell Transplantation (HSCT) — NCT00141739.
- Registry record last updated 2017-01-30; status last verified 2016-12.
- Results first posted 2014-06-04.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes NCT00141739, a completed phase 2, single-group study of etanercept added to standard GVHD prophylaxis for patients undergoing full intensity allogeneic hematopoietic stem cell transplantation. It lists 100 participants enrolled, no masking, and allocation as NA.
The primary outcome is the percentage of participants experiencing acute GVHD within 100 days, with incidence described for grades 2-4 and grades 3-4. The numerical primary result is not reported in the registry record. Secondary outcomes concern etanercept toxicity, idiopathic pulmonary syndrome, TNFR1 ratio by TBI status, and TNF polymorphisms.
Safety entries list 25 participants affected in the serious adverse event category and 89 in the other adverse event category, each among 100 at risk. The deaths field is null. Because the record has no comparator and does not report the primary outcome estimate, it supports a description of the study design and listed safety information, but not a direct comparative estimate of etanercept's effect.