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 Evaluation of Tabalumab Using Auto-Injector or Prefilled Syringe in Participants With Rheumatoid Arthritis (RA) (NCT01676701), a randomized phase 3 study. The primary outcome is Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Tabalumab After Loading Dose.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01676701 |
| Phase | Phase 3 |
| Condition | Rheumatoid Arthritis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 8 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Eli Lilly and Company |
| Results posted | Yes |
2. Clinical Question
Population
Participants with rheumatoid arthritis who had an inadequate response to methotrexate were the intended study population. The registry record lists an enrollment of 8. It does not report participant characteristics such as age, disease duration, or baseline disease activity.
Intervention
One group received tabalumab by auto-injector. The regimen began with a 180 mg loading dose at Week 0, given as 2 subcutaneous injections of 90 mg each, followed by 90 mg every 2 weeks through Week 12.
Comparator
The comparison group received the same tabalumab loading and follow-up regimen using prefilled syringes rather than auto-injectors. The central comparison is therefore between delivery devices, not between tabalumab and a different drug or placebo.
Primary question
The primary pharmacokinetic question was the maximum serum concentration, or Cmax, of tabalumab after the loading dose. Concentrations were scheduled for assessment on Days 4, 7, 9, 11, and 14. The registry record states that no participant outcome data were analyzed because the trial was terminated and the sample size was insufficient.
In practical statistical terms, the intended comparison concerned whether serum concentration profiles following the loading dose could be evaluated across the two device groups. Cmax is a measure of the highest concentration observed over a specified sampling period. The study also listed clinical response, disease activity, immunogenicity, device operation, and participant assessment outcomes as secondary measures, but analyzed results for these outcomes are not reported in the registry record.
3. Trial Design
This was a randomized, open-label, parallel-group phase 3 trial in rheumatoid arthritis. The registry record lists an enrollment of 8. Randomization was intended to assign participants to tabalumab delivered by auto-injector or by prefilled syringe. The record does not report the allocation ratio, the randomization procedure, or the method used to conceal assignments. Masking was listed as none, so the study was not described as blinded.
Both groups were scheduled to receive the same tabalumab dose and timing. At Week 0, the loading dose was 180 mg, administered as 2 subcutaneous injections of 90 mg each. The regimen then specified a 90 mg injection every 2 weeks through Week 12. The intended distinction between groups was the device used for administration. The brief description also notes an optional 40-week safety extension after the treatment period.
The study began in 2012-09, and the listed primary completion date was 2013-08. Its status is terminated. The registry record does not give further detail about the reason for termination beyond stating that no participant data were analyzed for the primary outcome because of termination and insufficient sample size. The timing and conduct of the optional safety extension for individual participants are not reported in the registry record.
The primary outcome was pharmacokinetic: maximum serum concentration after the loading dose, with planned sampling on Days 4, 7, 9, 11, and 14. Listed secondary outcomes included ACR measures, DAS28-CRP, EULAR-28 response, anti-tabalumab antibodies, operation failures, and a questionnaire about subcutaneous administration. A randomized parallel design can support a direct comparison between the assigned device groups, but the record does not report analyzed outcome data with which to make that comparison.
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 study was to include a 12-week treatment period, optional 40-week safety extension, and post-treatment follow-up (at least 24 weeks). At the time of early study termination, all participants who had received tabalumab discontinued dosing and then completed the post-treatment follow-up period. No one entered the 40-week safety extension period.
Overall Study
| Stage | Tabalumab Auto-Injector | Tabalumab Prefilled Syringe |
|---|---|---|
| STARTED | 4 | 4 |
| Received at Least 1 Dose of Study Drug | 4 | 4 |
| Completed Post-Treatment Follow-Up | 4 | 4 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 4 | 4 |
Reasons for not completing this period:
| Reason | Tabalumab Auto-Injector | Tabalumab Prefilled Syringe |
|---|---|---|
| Protocol Violation | 1 | 0 |
| Sponsor Decision | 3 | 4 |
Analysis population for the primary outcome, as defined in the registry: No participant had outcome measure data analyzed due to the termination of the trial and an insufficient sample size.
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: Randomized participants who received at least 1 dose of study drug.
| Characteristic | Unit | Tabalumab Auto-Injector | Tabalumab Prefilled Syringe | Total |
|---|---|---|---|---|
| Participants analysed | 4 | 4 | 8 | |
| Age, Customized: 43.3 to 65.4 years | participants | 4 | 4 | 8 |
| Sex: Female, Male: Female | Participants | 3 | 3 | 6 |
| Sex: Female, Male: Male | Participants | 1 | 1 | 2 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 | 1 | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 4 | 3 | 7 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 1 | 1 |
| Race (NIH/OMB): White | Participants | 4 | 3 | 7 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Region of Enrollment: United States | Participants | 4 | 4 | 8 |
6. Primary Endpoint
The registry lists the primary outcome as Pharmacokinetics (PK): Maximum Serum Concentration (Cmax) of Tabalumab After Loading Dose, measured over Days 4, 7, 9, 11, and 14 after loading dose administered.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the maximum serum concentration, or Cmax, of tabalumab after the loading dose. Serum concentration is a pharmacokinetic measure: it describes the amount of drug measured in the blood at scheduled sampling times. Cmax identifies the highest concentration observed over the measurement period. The record specifies sampling on Days 4, 7, 9, 11, and 14 after the loading dose.
As a general statistical concept, Cmax can help describe the peak concentration reached after a dose. Comparing this measure across administration devices can address whether the observed concentration profiles differ when the same drug regimen is delivered in different ways. It is one aspect of pharmacokinetics, not a complete description of exposure over time, clinical response, or safety.
The registry record does not report a Cmax estimate, a measure of variability, a confidence interval, or a statistical comparison between the device groups. It explicitly states that no participant outcome data were analyzed for this endpoint because the trial was terminated and the sample size was insufficient. Consequently, the endpoint's planned role can be described, but its value and the precision of any device comparison cannot be assessed from the reported results.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The intended inferential comparison was between two ways of administering tabalumab: an auto-injector and a prefilled syringe. Both groups had the same stated dosing schedule. The primary pharmacokinetic measure was Cmax following the loading dose, with sampling scheduled from Day 4 through Day 14 at the listed time points.
The principal interpretive fact is that the registry record reports no analyzed participant data for the primary outcome. It attributes this to trial termination and insufficient sample size. Thus, there is no reported group estimate, estimated difference, uncertainty interval, or test result for Cmax. The record does not establish whether the two devices produced similar or different maximum serum concentrations. That is an absence of an analyzed comparison, not evidence that the measurements were equivalent.
The registry record lists ten outcome measures, including several clinical response and disease activity measures, antibody development, operation failures, and participant assessment. It does not report analyzed results for these outcomes. Without outcome estimates and their uncertainty, the listed secondary measures cannot support a conclusion about response, device performance, or the relative safety of the administration methods.
Safety figures are recorded separately by group and period. The registry lists zero serious adverse events for each treatment-period and post-treatment follow-up group. It lists one other adverse event for the auto-injector post-treatment follow-up period, and zero for the other listed group-period entries. These counts are descriptive; the registry record does not report a statistical comparison of adverse events. The deaths fields are not reported in the registry record. These sparse counts should not be treated as precise estimates of event risk or as evidence of comparable safety.
Randomization describes the planned allocation method, but randomization alone does not supply an answer when the outcomes are not analyzed. The small listed enrollment and termination are important context for interpreting the lack of findings. Statistical significance cannot be assessed because no primary-outcome test result is reported. Likewise, no conclusion about the size or direction of a possible device difference can be drawn. The record documents the comparison that was intended and the absence of analyzed results, rather than a positive or negative finding about either device.
9. Statistical Methods Explained
What does randomization contribute?
In general, randomization assigns participants to study groups using a chance-based process. Its purpose is to reduce systematic differences between groups at the point of assignment, so that an outcome comparison can be interpreted as a comparison of the assigned interventions under the study conditions. It does not guarantee that groups will be alike in every characteristic, especially in a small study, and it cannot compensate for missing outcome analyses.
This trial is listed as randomized, parallel, and unmasked. The parallel design means participants were assigned to one device group rather than being described as switching between devices. The record does not describe the randomization sequence, allocation concealment, or analysis method. Since masking was listed as none, participants and study personnel were not described as blinded to the administration device.
What does Cmax measure?
As a general pharmacokinetic concept, serum concentration is a measurement of drug present in the blood at a sampling time. Cmax is the highest observed concentration in the specified assessment period. It can characterize a peak in the concentration profile, while other pharmacokinetic measures may describe different features, such as concentration over time. The registry record names Cmax as the primary endpoint and schedules measurements on Days 4, 7, 9, 11, and 14 after loading dose administration.
A Cmax estimate ordinarily needs observations from participants and a defined approach to summarizing those observations. A comparison between groups would also need an estimate of the contrast and its uncertainty. The registry record reports none of these analyzed quantities and says no participant outcome data were analyzed for the primary measure. Therefore, no group-level pharmacokinetic result can be interpreted from the record.
How should precision be understood?
In general, a confidence interval expresses the uncertainty around an estimate under a statistical model and analysis procedure. A narrower interval indicates greater precision under those assumptions; a wider interval indicates less precision. An interval does not, by itself, establish that a difference matters clinically or that the model assumptions are appropriate. Here, no Cmax estimate or confidence interval is reported, so the precision of a device comparison is not available.
A p-value, when reported, describes how compatible data are with a specified null hypothesis under the test assumptions. It is not a measure of the probability that a treatment works, nor does it convey the magnitude of a difference. The registry record does not report a p-value or a primary-outcome test. There is consequently no statistical significance result to interpret.
What do the planning assumptions mean?
The statistical planning description identifies a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. It describes sample-size illustrations based on a stated fraction of an observed effect. Such illustrations are planning scenarios: they describe participant counts that would be associated with specified assumptions, not an observed property of this trial. They are not observed power. No sample-size justification for the original trial is reported in the registry record.
Because no primary outcome was analyzed, an observed Cmax effect is not reported. The specific effect fraction and planning counts are not reported in the registry record. Any planning illustration should therefore be distinguished from evidence generated by participants in this trial. It cannot fill the gap left by absent outcome estimates or establish the precision that this study achieved.
Why can small samples be difficult to interpret?
As a general statistical matter, limited data often yield imprecise estimates, and uncommon outcomes may be observed rarely or not at all. A zero count in a small group does not show that the underlying event probability is zero. It may reflect limited observation, chance, or the study's follow-up and recording process. Conversely, a small nonzero count does not establish a stable difference between groups. These general cautions apply to the sparse adverse-event counts recorded for this trial.
The record's statement that the sample size was insufficient is directly relevant to the unavailability of the primary outcome analysis. It does not supply an estimate of how imprecise a hypothetical comparison would have been, because there is no reported estimate or interval. More generally, missing analysis is not the same as a non-significant result: a non-significant result would require an analyzed comparison and a reported test or uncertainty measure.
What can the design support?
In principle, a randomized comparison using the same regimen in both groups can focus the comparison on the delivery device. The open-label design is relevant to outcomes that may involve judgments or participant reports, such as a questionnaire about administration. The registry record does not describe procedures to limit measurement bias or give an analysis plan for these outcomes. Most importantly, the reported absence of analyzed participant outcomes prevents an empirical comparison of the devices for the listed endpoints.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists multiple outcome measures: a primary pharmacokinetic measure and secondary measures covering ACR response, disease activity, antibodies, operation failures, and administration assessment. When a study tests many outcomes, the chance of at least one apparently unusual result can increase if each is interpreted without accounting for the number of comparisons. As a general statistical approach, researchers may define a hierarchy of outcomes or adjust inference to address multiple testing. The registry record does not report a multiplicity strategy, so it is not possible to determine how any secondary comparisons were intended to be interpreted.
The registry record states that no participant outcome data were analyzed for the primary endpoint because the trial was terminated and the sample size was insufficient. It does not report analyzed results for the listed secondary outcomes. The specific analysis populations, handling of missing measurements, and rules for exclusions are not reported in the registry record. There is also no reported account of whether participants completed the planned concentration sampling or entered the optional safety extension.
Missing outcome data and unperformed analyses are different issues. In general, a missing-data method addresses how incomplete observations are handled within an analysis; it cannot create an observed treatment comparison when outcome data were not analyzed. The registry record does not describe imputation, sensitivity analyses, or an intention-to-treat or per-protocol analysis population. No conclusion about the effect of missingness on an estimate is possible because no such estimate is reported.
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 |
|---|---|---|---|
| Tabalumab Auto-Injector (Treatment Period) | 0 | 4 | 0.0% |
| Tabalumab Auto-Injector (Post Treatment Follow-Up Period) | 0 | 4 | 0.0% |
| Tabalumab Prefilled Syringe (Treatment Period) | 0 | 4 | 0.0% |
| Tabalumab Prefilled Syringe (Post Treatment Follow-Up Period) | 0 | 4 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tabalumab Auto-Injector (Treatment Period) | 0 of 4 |
| Tabalumab Auto-Injector (Post Treatment Follow-Up Period) | 1 of 4 |
| Tabalumab Prefilled Syringe (Treatment Period) | 0 of 4 |
| Tabalumab Prefilled Syringe (Post Treatment Follow-Up Period) | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tabalumab Auto-Injector (Treatment Period) | Tabalumab Auto-Injector (Post Treatment Follow-Up Period) | Tabalumab Prefilled Syringe (Treatment Period) | Tabalumab Prefilled Syringe (Post Treatment Follow-Up Period) |
|---|---|---|---|---|---|
| Gastric Infection | Infections and infestations | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 |
The adverse-event figures are separated by treatment group and by treatment period versus post-treatment follow-up. For each listed group-period entry, the registry reports 4 at risk for serious events and 0 affected. For other adverse events, it reports 4 at risk in each entry; the auto-injector post-treatment follow-up entry has 1 affected, while the other listed entries have 0 affected. These are counts recorded for the stated periods, not a statistical comparison between devices.
The serious-event counts are zero in all listed entries, but zero observed events do not prove that the underlying risk is absent. The event counts are sparse, and the record does not provide an uncertainty interval or comparative test. The single count under other adverse events during auto-injector follow-up should be read as a descriptive registry count, not as evidence that the device caused the event or that its risk differs from the syringe group.
Deaths are not reported in the registry record. No serious adverse event terms are listed. The record does not provide further details about event descriptions, timing, or causal attribution, so these cannot be inferred from the counts alone.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized comparison was planned between tabalumab administered by auto-injector and tabalumab administered by prefilled syringe. The regimens had the same stated loading dose and subsequent dosing schedule. The planned primary measure was Cmax after the loading dose, with serum sampling at specified time points through Day 14.
It does not establish whether the devices yielded similar or different serum concentrations. No participant outcome data were analyzed for the primary endpoint, and no estimate, uncertainty interval, or test result is reported. The listed secondary outcomes likewise have no analyzed results reported in the registry record. The absence of results must not be interpreted as a finding of no difference, equivalence, or lack of effect.
The adverse-event record contains descriptive counts by period and device group. The zero serious-event counts and the sparse counts for other events do not provide a precise comparative safety assessment. Deaths are not reported in the registry record, and event details beyond the listed counts are not available.
In general, an under-informative or incomplete trial record can still clarify what investigators intended to measure and how groups were to be compared. It cannot answer the study question without analyzed observations. For this trial, termination and the stated insufficient sample size explain why the primary outcome analysis is absent, but the registry record does not provide additional detail on termination. Any conclusion about pharmacokinetic comparability, clinical response, device usability, or relative safety would go beyond the reported results.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between a study question and an empirical result. Its design identifies a focused comparison: the same tabalumab regimen delivered with two different devices. The primary pharmacokinetic endpoint and scheduled serum sampling show what the planned assessment was intended to capture. Yet a clear question and a randomized design do not produce an answer when participant outcomes are not analyzed.
The registry record makes the limitation explicit: the trial was terminated, the sample size was insufficient, and no participant data were analyzed for the primary outcome. That statement is more informative than treating the absent result as a null finding. It tells readers that the available record cannot quantify a device contrast or its precision. It also illustrates why a report should distinguish between an estimate near zero and an estimate that was never produced.
The trial also highlights the limits of sparse safety counts. Counts can describe recorded events in each period, but without enough information and an analysis they do not establish comparative risk. General planning calculations, when used, answer hypothetical design questions under stated assumptions; they do not replace trial observations or demonstrate observed power.
For biostatisticians and clinical researchers, the key lesson is to align interpretation with the evidence actually reported. Design features describe intended inference; analyzed estimates and uncertainty describe what the observed data support. In this record, the former are documented more fully than the latter.
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 central limitation is the absence of analyzed participant outcomes. The registry record attributes the lack of primary outcome data to termination and insufficient sample size. Without a Cmax estimate, a group contrast, or an uncertainty measure, the intended pharmacokinetic comparison cannot be evaluated.
The listed enrollment is 8, and the adverse-event entries give small at-risk counts for each group and period. These counts allow a limited descriptive account only. They do not provide a precise assessment of uncommon harms or a reliable comparison between devices. The deaths fields are not reported in the registry record, and serious event terms are not listed.
The trial was unmasked. That design feature may be relevant to outcomes involving participant experience or assessment, including the administration questionnaire, although no results are reported and the registry record does not describe bias-control procedures. Details about randomization methods, allocation concealment, analysis populations, missing-data handling, and outcome-analysis methods are not reported in the registry record.
The record lists a range of secondary outcomes but does not report analyzed findings for them. It also does not report a multiplicity strategy or the original sample-size justification. The termination status and stated insufficiency of sample size limit interpretation, while the record does not give further details about the termination or individual follow-up. These gaps prevent conclusions about the reason for missing analyses beyond what the registry states.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Evaluation of Tabalumab Using Auto-Injector or Prefilled Syringe in Participants With Rheumatoid Arthritis (RA) — NCT01676701.
- Registry record last updated 2018-04-26; status last verified 2018-03.
- Results first posted 2018-04-26.
- 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
This phase 3 randomized, open-label, parallel trial compared tabalumab administered by auto-injector with tabalumab administered by prefilled syringe in participants with rheumatoid arthritis. The listed enrollment was 8. Both groups had the same stated loading dose and dosing through Week 12, and an optional 40-week safety extension was described.
The primary endpoint was Cmax after the loading dose, with sampling scheduled on Days 4, 7, 9, 11, and 14. The registry record states that no participant outcome data were analyzed for this endpoint because the trial was terminated and the sample size was insufficient. Analyzed results for the listed secondary outcomes are not reported in the registry record.
Serious adverse-event counts were zero in each listed group-period entry. One other adverse event was recorded in the auto-injector post-treatment follow-up entry; the other listed entries recorded zero. Deaths are not reported in the registry record. These figures are descriptive and do not establish a comparative safety result.