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 Beryllium Infliximab Study: Clinical Interventional Trial (NCT00111917), a randomized phase 1, phase 2 study. The primary outcome is A-a Gradient at End Exercise.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00111917 |
| Phase | Phase 1, Phase 2 |
| Condition | Berylliosis, Beryllium Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 13 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Maier, Lisa, M.D. |
| Results posted | Yes |
2. Clinical Question
Population
People with chronic beryllium disease, also identified in the registry under Berylliosis and Beryllium Disease. The study record lists an enrollment of 13, but the primary outcome has measurements reported for 7 participants in the infliximab group and 2 in the placebo group. The registry notes that accurate measurements were not obtained on all patients at both timepoints.
Intervention
Infliximab, also called Remicade in the registry summary, was administered by infusion at 0, 2, 6, 12, 18 and 24 weeks. The record describes an infliximab-to-placebo ratio of 3:1. It does not report an infliximab dose in the information recorded for this analysis.
Comparator
Placebo infusion. The registry describes a randomized, double-blind, placebo-controlled trial, with quadruple masking recorded for the study. The arm descriptions both contain the 3:1 infliximab-to-placebo ratio; further details about how that ratio was implemented are not reported in the registry record.
Primary question
The primary question was whether the change in end-exercise alveolar-arterial oxygen gradient differed between participants assigned to infliximab and those assigned to placebo after 28 week follow-up. The posted results give a median for each arm, but do not provide a between-arm estimate, confidence interval or p-value. The registry record therefore does not establish the precision or statistical significance of a treatment contrast.
3. Trial Design
The Beryllium Infliximab Study was registered as a randomized, parallel-group, placebo-controlled interventional trial in chronic beryllium disease. Its listed phases are PHASE1 and PHASE2. The record reports quadruple masking and identifies infliximab and placebo as the interventions. Randomization is intended, in general, to make treatment groups comparable in expectation; masking is intended to limit the influence of treatment knowledge on care, measurement or assessment. The registry record does not describe the specific randomization procedure or which roles were masked.
The planned infusion visits are listed at 0, 2, 6, 12, 18 and 24 weeks. The endpoint timeframe is after 28 week follow-up. The arm descriptions each state a 3:1 infliximab-to-placebo ratio, but do not clarify how that ratio relates to assignment within the two arms. No further details about the infusion dose or administration are reported in the registry record.
The study lists enrollment of 13 and has TERMINATED status. The registry lists a start of 2005-02 and primary completion of 2009-01. It does not report a reason for termination. These dates and status do not, by themselves, explain whether termination was related to recruitment, conduct, safety, efficacy, funding or another consideration.
The primary outcome is A-a Gradient at End Exercise, recorded as change in end-exercise A-a gradient and summarized by the median with standard error. The registry describes the A-a gradient as the difference between alveolar and arterial partial pressure of oxygen. The primary outcome population note cautions that accurate measures were not obtained on all patients at both timepoints. The record lists 4 outcome measures, while no analysis results are listed. Details of the intended statistical analysis, allocation implementation, and sample-size justification are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: the sponsor stopped the study due to slow recruitment
Overall Study
| Stage | Group 1 - Infliximab | Group 2 - Placebo |
|---|---|---|
| STARTED | 9 | 4 |
| COMPLETED | 8 | 3 |
| NOT COMPLETED | 1 | 1 |
Reasons for not completing this period:
| Reason | Group 1 - Infliximab | Group 2 - Placebo |
|---|---|---|
| Withdrawal by Subject | 1 | 1 |
Analysis population for the primary outcome, as defined in the registry: Accurate measures were not obtained on all patients at both timepoints.
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 | Infliximab | Control | Total |
|---|---|---|---|---|
| Participants analysed | 9 | 4 | 13 | |
| Age, Continuous | years | 54.63 (46 to 65) | 69.75 (67 to 74) | 56.5 (46 to 74) |
| Sex: Female, Male: Female | Participants | 4 | 1 | 5 |
| Sex: Female, Male: Male | Participants | 5 | 3 | 8 |
6. Primary Endpoint
The registry lists the primary outcome as A-a Gradient at End Exercise, measured over after 28 week follow-up. The Alveolar-arterial gradient (A-a gradient), is a measure of the difference between the alveolar partial pressure (A) of oxygen and the arterial (a) partial pressure of oxygen.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Standard Error |
| Unit | mmHg |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is change in the alveolar-arterial oxygen gradient, or A-a gradient, measured at end exercise. The registry defines this gradient as the difference between alveolar partial pressure of oxygen and arterial partial pressure of oxygen. It is expressed in mmHg. The measurement is intended to characterize the relationship between oxygen in the air spaces of the lungs and oxygen measured in arterial blood; the registry summary also describes assessment of oxygen exchange during exercise.
A change score compares a participant’s follow-up measurement with a baseline measurement. However, the record does not specify the subtraction convention, so the direction represented by a positive or negative change cannot be verified from the listed information alone. It also does not give a clinically important threshold for interpreting the size of a change.
The endpoint is summarized using a median and standard error. The median describes the midpoint of the observed values, rather than their arithmetic average. A standard error concerns uncertainty in an estimated summary; it is not the same as a standard deviation, which describes variation among individual measurements. The registry does not explain how the standard errors were calculated or provide confidence intervals.
The timeframe is after 28 week follow-up. The record explicitly notes that accurate measures were not obtained on all patients at both timepoints. This matters because the primary endpoint requires usable measurements at both occasions. The registry does not report the reasons for missing or inaccurate measurements, or the method used to address them.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome summaries are a median change of 27.3 mmHg for infliximab, with standard error 10.56, and a median change of 94.17 mmHg for placebo, with standard error 18.73. The registry gives these results for 7 participants in the infliximab group and 2 in the placebo group. They are descriptive summaries of the recorded endpoint values. They do not, on their own, quantify a reliable treatment effect.
In particular, the record does not provide a formal between-group estimate, a confidence interval for that estimate, or a p-value. It is therefore not possible to use these entries to determine the range of treatment contrasts compatible with the data or to assess the result against a specified significance threshold. The standard errors reported alongside the arm medians are not a substitute for an interval around a between-group effect. The registry does not say how those errors were estimated.
The outcome is described as a change, but the registry does not state which subtraction order was used. Without that convention, the numerical direction should not be labelled as improvement or worsening based only on the posted values. A clinical interpretation would also require context about the meaning of a given change in this endpoint; such a threshold is not reported in the registry record.
The small amount of primary-outcome information is especially important when reading the contrast between the arms. The recorded endpoint counts are not the same as the study enrollment, and the registry notes that accurate paired measurements were not obtained for all patients. The placebo summary is based on 2 participants, so it describes a very limited set of observed values. The record does not explain whether missing measurements were related to participant characteristics, treatment assignment, outcome values or other factors.
The study is recorded as terminated, but the reason is not reported in the registry record. Termination alone cannot establish why the study ended or what its results mean. Nor does the record identify whether the posted endpoint summaries represent an analysis specified before the results were known. No analysis results are listed in the registry entry. Thus, the available numbers support a cautious description of the observed arm summaries, not a definitive claim about efficacy, absence of efficacy or clinical importance.
9. Statistical Methods Explained
Randomization assigns participants to treatment groups by chance. In general, this reduces systematic differences between groups at the point of assignment, although it cannot guarantee balance in a small study. Here, the registry records randomized allocation and parallel groups, with infliximab compared against placebo. The exact randomization sequence, allocation concealment, and handling of any departures from assigned treatment are not reported in the registry record.
What does masking contribute?
Masking means keeping knowledge of assigned treatment unavailable to specified people involved in a study. It can reduce the chance that expectations influence participant reporting, clinical care, outcome measurement or interpretation. The record labels masking as quadruple, but does not identify which roles were masked or describe how masking was maintained. The label should therefore be read as a registry design descriptor rather than a complete account of masking procedures.
What does a median summarize?
The median is the midpoint of a set of ordered observations: values on either side occur at or below and at or above that midpoint. It can be a useful summary when a distribution is skewed or affected by extreme observations. It does not show the full distribution, and two groups can have the same median while differing in other aspects of their data. The posted primary endpoint is reported as a median for each arm, rather than as a mean.
How should a standard error be read?
In general, a standard error describes the uncertainty of an estimated statistic across repeated samples under a statistical model. It is not a measure of the spread of individual participant observations. The registry reports standard errors of 10.56 and 18.73 alongside the arm medians, but does not state how those standard errors were obtained. Standard errors alone do not supply a confidence interval or a test of the difference between arms. A method designed for the reported statistic and study design is needed to make those inferences.
Why does the between-group estimate matter?
A treatment comparison is usually expressed as an estimate of the difference between groups, together with an uncertainty measure such as a confidence interval and, where relevant, a test result. The two arm-specific medians are not themselves that estimate. The registry does not post a between-arm estimate, confidence interval or p-value for this endpoint. It is not appropriate to construct one from the posted summaries without assumptions about the data and analysis method, particularly with small and unequal endpoint counts and an outcome reported as a median.
What does a confidence interval communicate?
In general, a confidence interval describes a range of values compatible with the data under a specified statistical procedure. Its width communicates precision: a wider interval indicates less precise estimation. A confidence interval is not the probability that a fixed treatment effect lies in the particular interval. Because the registry does not report an interval for the treatment contrast, its precision cannot be assessed directly from the posted outcome results.
Why can over-dispersion matter?
In general, over-dispersion occurs when observed variability exceeds what a chosen statistical model assumes. If a model underestimates variability, its standard errors may be too small and its intervals too narrow. The record does not identify a count model or report an over-dispersion assessment for this continuous endpoint. The general issue is relevant whenever a statistical model is used, but there is no basis in the registry entry to say that over-dispersion occurred in this trial.
What do the planning assumptions mean?
The registry describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms and a normal approximation. It states that the effect to detect is a specified fraction of the observed effect. Such sample-size calculations are planning illustrations, not observed power and not evidence that the trial had adequate power. The registry record does not report a trial-specific sample-size justification, and no numerical planning targets are listed in the registry record for this analysis. Any planning illustration based on an observed effect also inherits uncertainty in that effect estimate.
10. Multiplicity, Missing Data and Analysis Populations
The record lists 4 outcome measures, but identifies the A-a gradient as the primary outcome summarized in the posted results. No secondary outcome results are listed. The registry records 0 analyses. It does not report a multiplicity strategy, such as a hierarchy of outcomes, adjustment for multiple comparisons, or a designation of secondary analyses as exploratory. Without such information, the approach to multiplicity cannot be evaluated. Multiple outcome testing can increase the chance of a false-positive finding when results are interpreted without an appropriate analysis plan; this is a general statistical concern, not evidence that a particular error occurred in this trial.
Missing endpoint data are a central limitation. The primary outcome note says accurate measures were not obtained on all patients at both timepoints. A change score requires measurements at baseline and follow-up, so some participants could not contribute an accurate paired result. The registry does not report why those measurements were unavailable, how many were missing at each timepoint, or whether missingness differed by assigned arm or participant characteristics. It also does not describe an imputation method, sensitivity analysis, or other approach to missing data.
The endpoint summaries are based on 7 participants in the infliximab group and 2 in the placebo group, while the listed study enrollment is 13. These counts should not be treated as interchangeable: the endpoint population is explicitly limited by measurement availability. No analysis population definition is reported, such as intention-to-treat or per-protocol, and the registry does not explain how participants were handled after assignment if they did not contribute an endpoint measurement.
Because reasons for missingness and the analysis population are not reported, the extent to which the observed summaries represent all randomized participants cannot be determined from this record. A complete interpretation would need the prespecified analysis approach and transparent accounting of outcome availability.
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 |
|---|---|---|---|
| Group 1 - Infliximab | 3 | 8 | 37.5% |
| Group 2 - Placebo | 1 | 3 | 33.3% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Group 1 - Infliximab | 0 of 8 |
| Group 2 - Placebo | 0 of 3 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1 - Infliximab | Group 2 - Placebo |
|---|---|---|---|
| Acute cholecystitis | Hepatobiliary disorders | 1 of 8 | 0 of 3 |
| Nausea, vomiting | Gastrointestinal disorders | 1 of 8 | 0 of 3 |
| liver function levels | Hepatobiliary disorders | 1 of 8 | 0 of 3 |
| Kidney stone | Renal and urinary disorders | 0 of 8 | 1 of 3 |
Serious events with the highest arm-level rate: kidney stone (33.3%), acute cholecystitis (12.5%), nausea, vomiting (12.5%), liver function levels (12.5%).
The registry reports serious adverse events for the groups labelled Infliximab and Placebo. In the infliximab group, 3 of 8 participants at risk are recorded as affected by a serious adverse event; in the placebo group, 1 of 3 participants at risk are recorded as affected. These are descriptive safety counts. They do not establish that an event was caused by treatment, and the registry does not provide a causal assessment for these entries.
For other adverse events, the record reports 0 affected among 8 at risk in the infliximab group and 0 affected among 3 at risk in the placebo group. The registry lists serious-event terms with percentages: Kidney stone, 33.3%; Acute cholecystitis, 12.5%; Nausea, vomiting, 12.5%; and liver function levels, 12.5%. The information available does not make clear how these terms map to treatment groups or what denominator each percentage uses, so the percentages should not be used to infer comparative risks.
Deaths are recorded as null for both groups. This means death information is not reported in the registry record; it should not be interpreted as zero deaths. The safety counts are limited and descriptive, and the record does not give event timing, severity details beyond the serious-event classification, or a comparison adjusted for differences in the groups.
12. What the Result Does, and Does Not, Mean
The registry describes a randomized, masked comparison of infliximab and placebo in chronic beryllium disease, with change in end-exercise A-a gradient as the primary endpoint. The posted results give arm-level medians and standard errors, but not a treatment contrast with an interval or test result. This distinction is essential: descriptive group summaries are not enough to establish the size, precision or statistical significance of a treatment effect.
The primary endpoint values are based on limited numbers of participants, and the registry states that accurate measurements were not available for all patients at both timepoints. The record does not explain the missing measurements or how they were handled. The direction of change is also not defined by a stated subtraction convention. Consequently, the values cannot be confidently translated into a claim of improvement or worsening based solely on the registry entries.
The study status is TERMINATED, but no reason for termination is reported in the registry record. That status should not be treated as evidence for or against an effect. Likewise, the serious adverse event counts and listed event terms are descriptive safety information; they do not by themselves establish causation or comparative safety.
In general, a treatment conclusion depends on more than whether arm summaries differ. It requires a clearly defined estimand, an appropriate comparison, uncertainty estimates, attention to missing data and a clinically meaningful interpretation of the endpoint. Those elements are not all reported for this study. The available record can therefore support a careful account of what was measured and which summaries were posted, but not a definitive efficacy or safety conclusion.
These limitations do not show that the intervention has no effect, nor do they show that it has an effect. They describe what can and cannot be inferred from the posted registry results. Additional analysis details, including a prespecified statistical plan and transparent handling of unavailable measurements, are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable because it combines a randomized, masked design with a primary endpoint for which the registry reports only a small amount of usable outcome information. Randomization is a strong design principle for reducing systematic confounding, but its benefits do not replace careful reporting of the outcome analysis. In particular, a between-group estimate and its uncertainty are needed to describe how precisely the treatment contrast is known.
The primary outcome is reported as a median change with standard error. Those summaries can be informative, but they do not provide the distribution of individual observations or the uncertainty around the difference between arms. The unequal and limited endpoint counts, together with the explicit note about unavailable accurate paired measurements, make transparent reporting of missingness especially important. The registry does not provide the missing-data strategy or analysis-population definition.
The entry also illustrates why trial status and results must be interpreted separately. TERMINATED is a status, while the reason is not reported in the registry record. It cannot serve as a substitute for a statistical analysis or explain the observed endpoint summaries.
Finally, the registry describes sample-size planning assumptions but does not report a trial-specific justification or numerical target values in the information used for this analysis. General planning calculations are not observed power and do not establish that a study can answer its clinical question. The main statistical lesson is the need to distinguish design features, descriptive results, inferential comparisons and the limits created by incomplete outcome data.
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 record acknowledges that accurate measurements were not obtained on all patients at both timepoints. It does not report the reasons, timing or arm-specific pattern of those unavailable measurements, nor the method used to address them. Since the endpoint is a change between baseline and follow-up, the absence of a reliable measurement at either timepoint can prevent inclusion in the paired summary. The posted endpoint counts therefore represent a subset of the enrolled study population.
The record does not state the subtraction convention for the change score. As a result, the direction of a numerical change cannot be interpreted unambiguously from the registry description. It also does not specify a threshold for a clinically important change, or provide a confidence interval or p-value for the between-arm contrast. The standard errors are reported for arm medians, but their calculation method is not described.
The registry gives a terminated status without a reason. It does not report the statistical analysis plan, a trial-specific sample-size justification, a defined analysis population, or an approach to multiplicity. The record lists 4 outcome measures but reports no secondary outcome results and 0 analyses. The relationship between the 3:1 ratio in each arm description and assignment is not clarified. The dose and additional details of the intervention are not reported in the record information used for this analysis.
For safety, the group-level serious-event counts are descriptive, and the listed event-term percentages are not clearly tied to a group or denominator. Death entries are null, so they are not interpretable as zero. Together, these omissions limit both statistical and clinical interpretation of the posted findings.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Beryllium Infliximab Study: Clinical Interventional Trial — NCT00111917.
- Registry record last updated 2016-06-02; status last verified 2016-03.
- Results first posted 2014-09-25.
- 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
NCT00111917 is a randomized, parallel, placebo-controlled interventional trial of infliximab for chronic beryllium disease. The registry lists PHASE1 and PHASE2, quadruple masking, enrollment of 13, and TERMINATED status. The study started in 2005-02 and has a primary completion date of 2009-01; the reason for termination is not reported in the registry record.
The primary outcome is change in end-exercise A-a gradient after 28 week follow-up, summarized by arm medians and standard errors. The posted endpoint summaries are based on 7 participants receiving infliximab and 2 receiving placebo. The registry notes that accurate measurements were not obtained on all patients at both timepoints. It does not report a between-arm estimate, confidence interval, p-value, analysis population, or missing-data method.
Serious adverse events are reported for both groups, while death information is not reported. No secondary outcome results are listed, and no analysis results are recorded. The findings therefore offer limited descriptive information and do not support a precise inferential conclusion from the registry record alone.