Erythrocytes-Mediated Delivery Of Dexamethasone 21-Phosphate In Steroid-Dependent Ulcerative Colitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Erythrocytes-Mediated Delivery Of Dexamethasone 21-Phosphate In Steroid-Dependent Ulcerative Colitis (NCT01171807), a randomized phase 2 study. The primary outcome is The Proportion of Patients Responders to Dex 21-P vs Placebo.

2. Clinical Question

3. Trial Design

This was a randomized, parallel-group Phase 2 trial comparing Dex 21-P with placebo. Masking was listed as none, so the trial was not reported as blinded. The registry record lists enrollment as 33 and status as completed. The recorded start date is 2003-07-22, and the primary completion date is 2007-05-15. These registry entries describe the planned structure and recorded conduct; they do not establish that all planned procedures or assessments were completed by every participant.

The title focuses on erythrocyte-mediated delivery of dexamethasone 21-phosphate in steroid-dependent ulcerative colitis, while the official title refers to patients with Crohn's disease or ulcerative colitis. The record also describes a clinical subgroup of patients with mesalazine-refractory ulcerative colitis. The primary endpoint description refers to chronic and steroid-dependent IBD patients as well as mesalazine-refractory ulcerative colitis patients, with different stated end-of-treatment timeframes. The registry record does not provide enough information to reconstruct all subgroup-specific assignment or assessment details.

Both arms involved repeated treatment procedures. The listed schedules refer to administration every 15 or 30 days and a total of 3 or 6 procedures, with 6 monthly procedures specified for steroid-dependent IBD patients. The intervention descriptions are incomplete for the mesalazine-refractory subgroup, so its full schedule cannot be established from the registry record. Random allocation supports a between-arm comparison in principle, but the absence of masking is relevant when interpreting outcomes that involve clinical assessments or treatment decisions. The record does not report the allocation method, concealment procedures, or further details of trial conduct.

The registry record lists one primary outcome and several secondary outcomes, including cortisol, inflammatory markers, endoscopic findings, and adverse events. It does not report a complete analysis plan, the method used to handle missing observations, or the approach to multiplicity across outcomes. Those omissions limit what can be concluded about how the design was translated into the statistical 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.

Before assignment: Thirty-three (33) outpatients were enrolled into the study: nineteen subjects were steroid dependant (8 and 11 affected from Chron's Disease and Ulcerative Colitis, respectively) while 14 were patients with Ulcerative Colitis refractory to mesalazine.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Population: subjects who underwent at least one treatment procedure

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: Intention to Treat population (ITT): subjects who underwent at least one treatment procedure

6. Primary Endpoint

The registry lists the primary outcome as The Proportion of Patients Responders to Dex 21-P vs Placebo, measured over From baseline to End of treatment = 6 weeks ± 10 days (in chronic and steroid dependent IBD patients) or 28 weeks ± 5 days (in mesalazine refractory UC patients).

The primary endpoint was the proportion of patients classified as responders to Dex 21-P or placebo. A participant was a responder at the end of the study if either disease remission or marked improvement was recorded, and oral steroid therapy had been withdrawn from at least the second treatment procedure. The remission definition used a Powell-Tuck index of 3 or less or a CDAI below 150. The marked-improvement definition required a decrease of at least 5 points in Powell-Tuck or 150 points in CDAI, together with steroid withdrawal.

This endpoint combines a change in disease activity with a treatment-management condition. It therefore does not count a symptom or score change alone as response: withdrawal of oral steroids is also required. The registry record describes Powell-Tuck as a seven-item score, with higher scores indicating worse ulcerative-colitis activity. It describes CDAI as an index combining subjective and objective parameters, with scores reflecting Crohn's disease activity.

A binary responder outcome can make a clinical trial question easier to express as the proportion meeting a prespecified composite definition in each arm. However, the classification depends on the chosen thresholds and on the steroid-withdrawal requirement. The registry record does not report participant-level score changes, the component contributions to response, or response counts by arm. It also does not report a numerical estimate of the primary between-arm comparison, so the observed response proportions and their precision cannot be assessed from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation begins by distinguishing the endpoint definition from the analysis result. Here, the endpoint is binary: each participant is classified as a responder or not a responder according to the stated clinical and steroid-withdrawal criteria. In general, a binary outcome can be summarized by the number and proportion of participants meeting the definition in each arm. A between-arm estimate can then describe the contrast, and a confidence interval can describe the uncertainty around that estimate. The registry record does not report the response counts, a contrast estimate, or a confidence interval for this primary outcome.

What does a binary responder outcome capture?

In general, converting an outcome to responder status makes the result depend on a threshold. Participants on opposite sides of a threshold are classified differently even if their underlying scores are close, while participants with different score changes can receive the same responder classification if both satisfy the criteria. This trial's rule is more than a score threshold: response also requires withdrawal of oral steroids from at least the second treatment procedure. That conjunction is important when interpreting what the endpoint represents.

The two disease-activity routes to response are not identical. One is remission, defined by the Powell-Tuck or CDAI criterion; the other is marked improvement, defined by a change from baseline in one of those measures. Both routes require steroid withdrawal. The registry record does not report how many responders, if any, qualified through each route or which disease measure was used for each participant. It therefore does not permit a decomposition of the composite into its components.

Why do denominators matter?

For a proportion, the denominator is the number of participants whose outcome contributes to the analysis. It should be clear whether that is everyone randomized, everyone treated, or only those with an observed endpoint. The registry defines its primary population as subjects who underwent at least one treatment procedure. That definition does not by itself tell the reader how many participants in each arm entered the primary analysis or how missing endpoint values were handled. Those details are not reported in the registry record.

In general, excluding participants without an observed endpoint can affect a comparison if outcome availability is related to treatment assignment or prognosis. Different missing-data assumptions can therefore lead to different estimates. A transparent report normally identifies the analysis population, the number with available outcomes in each arm, the missingness pattern, and the method used to address missing outcomes. The registry information does not report those details, so no missing-data sensitivity assessment can be reconstructed.

What does the registry say about the analysis?

The record lists one analysis but also states that the primary outcome has several categories or time points and was not reduced to one comparison. It does not give an inferential method, a model, an adjustment strategy, or a hypothesis-testing result for the responder endpoint. These omissions mean it is not possible to determine whether the sponsor used a particular test or model, or to compare a recalculation with the sponsor's own primary analysis.

General methods for a binary outcome may include a comparison of proportions, a risk difference, a relative measure, or a regression model. Which method is appropriate depends on the analysis plan, estimand, data structure, and assumptions. Naming these general options does not imply that any one was used in this trial. The registry record does not report enough to identify the sponsor's method or reproduce its analysis.

How should uncertainty be read?

In general, a confidence interval gives a range of values compatible with the data under the specified analysis procedure. It conveys precision as well as the point estimate: a wide interval indicates more uncertainty than a narrow interval. A p-value, when reported, addresses compatibility with a null hypothesis under a statistical model; it does not measure clinical importance or the probability that a treatment effect is true. Neither a confidence interval nor a primary-outcome p-value is reported in the registry record.

The absence of these statistics prevents assessment of whether the primary comparison was precise, whether it excluded effects of practical interest, or whether the data were compatible with effects in more than one direction. A non-significant result, if one had been reported, would not by itself establish equivalence. Conversely, a small p-value would not alone establish that an effect is important. These are general principles and are not claims about this trial's unreported result.

What does the planning information mean?

In general, sample-size calculations are planning tools that depend on assumptions about the effect to detect, variability or event frequency, significance level, allocation, and analysis method. They are not observed treatment effects, and they do not establish the power achieved after a trial has been completed. The registry record describes a planning illustration based on a fraction of the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It distinguishes participants per arm for non-time-to-event outcomes from total events for time-to-event outcomes.

The record does not state that this illustration was the trial's original design justification. It does not report the assumptions used for the trial's own planning or a sample-size justification in the registry information. Without the numerical planning outputs and the observed primary-outcome effect, the illustration cannot be used to infer a particular required enrollment, observed power, or adequacy of the trial's enrollment. General planning calculations should be read as conditional on their stated assumptions, not as a substitute for a precise effect estimate and its uncertainty.

Why does multiplicity matter?

When a study examines multiple outcomes, subgroups, time points, or definitions, the chance of at least one apparently notable result can increase if many comparisons are tested without an appropriate plan. In general, a prespecified primary endpoint and a clearly stated analysis hierarchy help readers distinguish confirmatory from exploratory comparisons. The registry lists several secondary outcomes and describes more than one clinical subgroup and timeframe. It does not report whether multiplicity was controlled, how outcomes were prioritized, or whether analyses were prespecified in a statistical plan. The multiplicity implications therefore cannot be quantified from the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary responder outcome alongside secondary measures of cortisol, ESR, CRP, endoscopic result, and treatment-emergent adverse events. It also describes distinct clinical populations and end-of-treatment timeframes. Examining several outcomes, subgroups, or time points can create multiplicity: in general, the more comparisons considered, the greater the opportunity for a seemingly notable finding to arise by chance. The record does not report a multiplicity adjustment, a testing hierarchy, or which comparisons were designated confirmatory. It is therefore not possible to determine how multiplicity was handled.

The primary population is described as the intention-to-treat population of subjects who underwent at least one treatment procedure. This is the registry's stated definition; it should not be assumed to mean all randomized participants. The record does not give arm-specific primary-analysis denominators, the number of missing primary outcomes, or the reasons for missingness. It also does not describe an imputation method, a sensitivity analysis, or another approach to participants without an observed outcome. Those details are not reported in the registry record.

In general, missing data can affect the estimated response proportion, particularly when the probability of an outcome being missing differs across arms or is related to the unobserved outcome. The direction and size of any bias cannot be inferred without information about missingness and the analysis assumptions. The posted record also does not report a full statistical analysis plan or explain whether the primary analysis followed an intention-to-treat principle beyond the stated population definition. These limitations prevent reconstruction of the analysis population and assessment of the robustness of the primary comparison.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: acute pancreatitis (8.3%).

The safety record gives separate counts for serious events, other events, and deaths in the safety population. For Dex 21-P, the record lists 0 participants with a serious adverse event among 21 at risk, and 11 with another reported adverse event among 21 at risk. For placebo, it lists 1 participant with a serious adverse event among 12 at risk, and 8 with another reported adverse event among 12 at risk. Deaths are listed as 0 in both groups. These are descriptive counts, not estimates of a causal treatment effect.

The record also identifies acute pancreatitis, with 8.3%, among the top serious terms. It does not establish from the information reported whether this term corresponds to the serious event in a particular arm, and it should not be assigned to an arm without that information. The registry lists secondary outcomes for participants experiencing at least one treatment-emergent adverse event, separated into steroid-related and not steroid-related events, but the displayed group counts do not provide those specific classifications.

Safety comparisons require caution because the groups are small and unequal in size, and because counts alone do not show timing, duration, severity, recurrence, or exposure-adjusted rates. The registry record does not provide enough detail to assess those features or to determine how adverse events were judged related to treatment. The counts describe what was recorded; they do not establish that a treatment caused or prevented an event.

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

The registry record establishes that a randomized, unmasked Phase 2 trial compared Dex 21-P with placebo and that its primary endpoint was a composite responder classification. The definition required remission or marked improvement in disease activity together with withdrawal of oral steroids from at least the second treatment procedure. This tells readers what the trial intended its primary endpoint to represent.

It does not, however, report a numerical primary-outcome comparison. Without arm-specific responder counts, analysis denominators, an effect estimate, or an uncertainty interval, the record cannot show the observed difference between Dex 21-P and placebo or how precisely that difference was estimated. The absence of a reported comparison must not be interpreted as a finding of no difference, equivalence, or benefit. It is an absence of outcome information in the registry record.

The endpoint is also composite. Even if the overall responder result were available, interpretation would depend on which component contributed to response. The registry does not report component-level results, so the relative contribution of disease-score improvement, remission, and steroid withdrawal cannot be evaluated. The different disease instruments used in the definition also reflect the trial's inclusion of ulcerative colitis and Crohn's disease populations; the record does not report a subgroup-specific primary comparison.

The safety counts offer limited descriptive information: the record lists serious and other adverse-event counts and no deaths in either group. They do not establish treatment causality or provide a complete assessment of event timing, severity, or attribution. The broader secondary outcome descriptions likewise do not constitute results.

In general, a completed trial can still leave important questions unanswered when the registry does not include outcome estimates and analysis details. The proper conclusion is therefore narrow: the record describes the comparison and its intended outcomes, but it does not supply enough primary efficacy information to quantify the observed treatment contrast or enough detail to determine its robustness.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of the difference between a trial's design and the results needed to interpret its central question. Randomization and a parallel-group comparison define a framework for comparing Dex 21-P with placebo. The responder definition identifies the outcome the trial intended to evaluate. But without response counts, denominators, or an effect estimate, the comparison cannot be quantified from the registry record.

The composite endpoint also illustrates how operational definitions shape statistical conclusions. Response combines a disease-activity threshold or improvement criterion with steroid withdrawal. Such a rule can reflect more than one aspect of a patient's course, but it also means an overall responder result would not reveal which component drove the classification. Component-level results and clear subgroup reporting would help readers understand what the binary outcome captures.

The trial includes more than one disease context and more than one timeframe. That makes transparency about populations, endpoint assessment, and multiplicity particularly important. In general, distinct subgroups and assessment times can support clinically focused questions, but they also require a clear analysis plan to prevent selective interpretation. The registry record does not describe such a plan or explain how multiplicity was handled.

The record's safety counts also show why descriptive event numbers should not be treated as causal comparisons. Counts are useful for reporting what was observed, but interpretation depends on denominators, event definitions, attribution, timing, and exposure. The listed information supports only a limited descriptive reading.

More broadly, this example underscores the value of complete registry results: prespecified outcome definitions are most useful when accompanied by arm-specific results, analysis populations, missing-data handling, uncertainty estimates, and methods. Those details enable readers to distinguish an inconclusive or imprecise estimate from an absent result. Here, the endpoint is defined, but the numerical primary comparison is not reported.

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.

Several limitations are specific to the registry information for this trial. The primary responder outcome is defined, but the record does not report response counts, arm-specific denominators, an effect estimate, or an uncertainty interval. It also notes that the primary outcome had several categories or time points and was not reduced to one comparison. Consequently, the primary contrast cannot be reconstructed or assessed for precision.

The clinical populations and assessment schedules are not fully described. The title emphasizes steroid-dependent ulcerative colitis, while the official title includes Crohn's disease or ulcerative colitis; the primary endpoint description also refers to mesalazine-refractory ulcerative colitis. The intervention descriptions provide some scheduling information but are incomplete for the subgroup-specific regimen. The record does not report subgroup-specific response results or enough information to compare the populations separately.

The trial was unmasked, which is relevant to clinical assessments and decisions such as steroid withdrawal. The registry information does not explain whether outcome assessors were masked, how the withdrawal criterion was applied, or how the allocation sequence was generated or concealed. These details are not reported in the registry record.

The analysis population is described as subjects who underwent at least one treatment procedure, but the record does not provide analysis denominators or explain how missing outcomes were handled. It does not report a full statistical analysis plan or its approach to multiplicity across the listed outcomes, subgroups, and timeframes. Thus, the effect of missing data and the statistical status of secondary comparisons cannot be assessed.

Safety reporting is also limited to counts and a serious-event term. The registry record does not provide the context needed to evaluate timing, duration, severity, attribution, or recurrence. These limitations restrict interpretation; they do not establish that any unreported event or analysis did or did not occur.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Erythrocytes-Mediated Delivery Of Dexamethasone 21-Phosphate In Steroid-Dependent Ulcerative Colitis — NCT01171807.
• Registry record last updated 2024-09-24; status last verified 2024-04.
• Results first posted 2024-09-24.
• 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

NCT01171807 is a completed, randomized, unmasked, parallel-group Phase 2 trial of Dex 21-P versus placebo. The registry lists enrollment as 33, a start date of 2003-07-22, and a primary completion date of 2007-05-15. The trial concerned inflammatory bowel disease, including steroid-dependent patients and patients with mesalazine-refractory ulcerative colitis.

The primary endpoint was the proportion of patients classified as responders by end of treatment. Response required remission or marked improvement in disease activity and withdrawal of oral steroids from at least the second treatment procedure. The primary population was described as subjects who underwent at least one treatment procedure.

The registry record does not report a numerical primary-outcome comparison. It lists secondary outcomes involving cortisol, ESR, CRP, endoscopic findings, and adverse events, but the information does not include numerical results for those outcomes. Safety counts include serious and other adverse events and deaths by arm; these support descriptive reporting only.