A Study of Belimumab in Subjects With Systemic Lupus Erythematosus: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Belimumab in Subjects With Systemic Lupus Erythematosus (NCT00410384), a randomized phase 3 study. The primary outcome is SLE Responder Index (SRI) Response Rate at Week 52.

2. Clinical Question

The clinical question is about a defined combination of changes in disease activity and worsening criteria, rather than a single symptom or laboratory measure. Participants who needed rescue SLE medication, dropped out, or lacked Week 52 data were classified as nonresponders for this primary outcome. The posted result therefore reflects both the response definition and the registry’s handling of these events.

3. Trial Design

The registry describes a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. It evaluated belimumab at 1 mg/kg and 10 mg/kg against placebo, with study treatment added to standard therapy. The planned study duration in the official title was 76 weeks. The registry lists an enrollment of 819 and a completed status.

The registry records a start date of 2006-12 and a primary completion date of 2009-09. These dates describe the record; they do not establish when every participant entered or completed follow-up. Further information about recruitment, follow-up by group, treatment adherence, or the timing of any changes to the protocol is not reported in the registry record.

The main endpoint was assessed at Week 52, while listed secondary outcomes include assessments at Week 24, Week 52, and Week 76. The primary analysis population was modified intention-to-treat, defined as randomized participants who received at least one dose. This differs from an analysis that includes every randomized participant regardless of treatment received. The registry’s specified nonresponder rule also means that rescue medication, withdrawal, and missing Week 52 outcome data affected the endpoint classification.

The registry record does not report the original sample-size justification, the trial’s prespecified statistical analysis plan, or whether interim analyses were planned or conducted. The planning figures discussed separately are illustrations based on the observed results, not evidence of the assumptions used when the study was designed.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on a modified intention-to-treat (MITT) population, defined as all subjects who were randomized and received at least 1 dose of study agent. Subjects who required rescue SLE medications were declared nonresponders, as were subjects who dropped out or were missing Week 52 data.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as SLE Responder Index (SRI) Response Rate at Week 52, measured over Baseline, 52 Weeks.

The primary outcome was the SLE Responder Index (SRI) response rate at Week 52, expressed as the percentage of participants meeting a composite definition. A responder needed a reduction of at least 4 points from baseline in the SELENA SLEDAI score, no worsening in the Physician’s Global Assessment (PGA), and no new BILAG A organ-domain score or two new BILAG B organ-domain scores compared with baseline.

The components capture different aspects of SLE status. SELENA SLEDAI combines 24 descriptors; a score of 0 indicates inactive disease, and the maximum theoretical score is 105. Scores greater than 20 are rare. PGA is a visual analogue scale from 0 to 3, with higher scores indicating greater severity as described in the registry. BILAG assigns a score for each of 8 organ domains, ranging from A to E, from severe disease to no disease.

A composite endpoint is used to define response across several measures at once. Requiring improvement in one component while also limiting worsening in others makes the response definition more specific than a change in SELENA SLEDAI alone. It also means the overall response rate depends on all parts of the definition and on the handling of missing outcomes. The registry classified participants who required rescue SLE medication, dropped out, or lacked Week 52 data as nonresponders.

7. Results Posted in the Registry

• Belimumab 1 mg/kg: 40.6% (110/271) versus 33.5% (92/275) on control; risk difference 7.1 percentage points (95% CI -0.9 to 15.2), risk ratio 1.21 (0.97–1.51); unadjusted two-proportion z-test p = 0.084.
• Belimumab 10 mg/kg: 43.2% (118/273) versus 33.5% (92/275) on control; risk difference 9.8 percentage points (95% CI 1.7 to 17.9), risk ratio 1.29 (1.04–1.60); unadjusted two-proportion z-test p = 0.019.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

SRI Response Rate at Week 76

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Belimumab 1 mg/kg: 39.1% (106/271) versus 32.4% (89/275) on control; risk difference 6.8 percentage points (95% CI -1.3 to 14.8), risk ratio 1.21 (0.96–1.52); unadjusted two-proportion z-test p = 0.100.
  • Belimumab 10 mg/kg: 38.5% (105/273) versus 32.4% (89/275) on control; risk difference 6.1 percentage points (95% CI -1.9 to 14.1), risk ratio 1.19 (0.95–1.49); unadjusted two-proportion z-test p = 0.136.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Belimumab 1 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Belimumab 10 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.

Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52.

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Belimumab 1 mg/kg: 42.8% (116/271) versus 35.3% (97/275) on control; risk difference 7.5 percentage points (95% CI -0.6 to 15.7), risk ratio 1.21 (0.98–1.50); unadjusted two-proportion z-test p = 0.071.
  • Belimumab 10 mg/kg: 46.5% (127/273) versus 35.3% (97/275) on control; risk difference 11.2 percentage points (95% CI 3.1 to 19.4), risk ratio 1.32 (1.07–1.62); unadjusted two-proportion z-test p = 0.007.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Belimumab 1 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Belimumab 10 mg/kg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Mean Change in Physician's Global Assessment (PGA) at Week 24.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Belimumab 1 mg/kg: mean -0.47 versus -0.49 on control; difference 0.02 (95% CI -0.09 to 0.13), standardized effect d = 0.03; z-test p = 0.724.
  • Belimumab 10 mg/kg: mean -0.44 versus -0.49 on control; difference 0.05 (95% CI -0.05 to 0.15), standardized effect d = 0.09; z-test p = 0.317.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Belimumab 1 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Belimumab 10 mg/kg and the control. The interval gives the range of effects that remain compatible with the data.

Across the posted secondary outcomes, the broad pattern is mixed by outcome and time point rather than a uniform shift across every measure. The response and disease-activity outcomes generally have higher reported proportions in the belimumab groups than in the placebo group, while the mean changes in PGA are close across groups. This pattern is broadly consistent with the direction of the primary response proportions, but secondary outcomes measure different features and do not independently establish the primary finding.

The registry lists Week 76 SRI response, Week 52 SELENA SLEDAI improvement, Week 24 PGA change, Week 24 SF-36 physical-component change, and prednisone reduction during Weeks 40 through 52 among the secondary outcomes. Results for SF-36 and prednisone reduction are not reported in the registry record. The secondary results that are posted include sponsor analyses for selected comparisons, but the registry record does not provide a complete analysis plan or explain how the many outcomes and comparisons were handled together.

General statistical explanation: when many outcomes or comparisons are examined, some may appear notable by chance even if there is no underlying effect for those outcomes. This is why unadjusted secondary p-values carry less weight than a prespecified primary analysis, especially when the multiplicity strategy is not reported. Secondary results can help describe consistency and generate questions, but they should not be treated as independent confirmation without considering their prespecification, analytic methods, and missing results.

The secondary outcomes also differ in scale: some are binary response percentages and others are mean changes. Their estimates cannot be ranked directly by numerical size. The record does not report enough detail to determine whether all listed secondary outcomes were tested under a formal hierarchy or whether any adjustment for multiple testing was applied.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• SRI Response Rate at Week 76
• Percent of Subjects With a ≥ 4 Point Reduction From Baseline in SELENA SLEDAI Score at Week 52.
• Mean Change in Physician's Global Assessment (PGA) at Week 24.
• Mean Change From Baseline in Medical Outcomes 36-Item Short Form Health Survey (SF-36) Physical Component Summary Score (PCS) at Week 24.
• Percent of Subjects Whose Average Prednisone Dose Has Been Reduced by ≥ 25% From Baseline to ≤ 7.5 mg/Day During Weeks 40 Through 52

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each participant is classified as a responder or nonresponder, and the group result is a response percentage. The registry’s responder definition combines improvement in SELENA SLEDAI with limits on worsening in PGA and BILAG. The analysis then compares the proportion meeting that definition in each belimumab group with the proportion in the placebo group.

What does a risk difference describe?

General statistical explanation: a risk difference subtracts the event proportion in one group from the event proportion in another. For this endpoint, the event is meeting the SRI response definition. A positive risk difference means that the response proportion is higher in the belimumab group than in the placebo group. The recalculated estimates are unadjusted comparisons based on the posted group summaries; they do not account for covariates through a regression model.

The recalculated risk differences are 0.071 for belimumab 1 mg/kg and 0.098 for belimumab 10 mg/kg, each compared with placebo. Their confidence intervals quantify uncertainty around those estimates. These are not the same measure as the odds ratios in the registry’s reported analyses. An odds ratio compares the odds of response between groups, while a risk difference compares response proportions directly. Because the measures use different scales, their numerical values should not be compared as if they were interchangeable.

Why is logistic regression used?

General statistical explanation: logistic regression is a method for modeling a binary outcome, such as responder versus nonresponder. It can produce an odds ratio for a group comparison and can incorporate adjustments if the model includes covariates. The registry identifies logistic regression and reports odds ratios, but the covariates and full model specification are not reported in the registry record. Those details should not be inferred from the method label alone.

The registry’s reported odds ratios are 1.54 for 10 mg/kg versus placebo and 1.36 for 1 mg/kg versus placebo. Their confidence intervals and p-values are the sponsor’s reported results. The unadjusted calculations are useful for understanding the posted group proportions, but they are not a replacement for the sponsor’s model. With a flagged discrepancy, the sponsor’s own analysis takes precedence.

What does a p-value contribute?

General statistical explanation: a p-value describes how compatible the observed data are with a specified null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it describe the size or clinical importance of an effect. The registry reports p-values for its logistic-regression comparisons, and the recalculation also reports unadjusted p-values. Since these come from different analyses, they should be kept distinct.

How does the analysis population affect the result?

The modified intention-to-treat population included randomized participants who received at least one dose. The registry specifies that participants who required rescue SLE medication, dropped out, or lacked Week 52 data were nonresponders. This rule assigns an outcome status for the primary analysis, but does not reveal how many participants were affected. Other missing-data procedures, such as imputation methods or sensitivity analyses, are not reported in the registry record.

General statistical explanation: a binary endpoint simplifies a complex clinical state into a response classification. This can make the result easier to interpret, but it depends on the threshold and component rules chosen. A change that falls short of the defined threshold does not count as a response, even if another measure changes. The registry record does not report additional analyses that vary the SRI definition.

11. Confidence Intervals and Precision

A confidence interval gives a range of values reasonably compatible with the data and the statistical method used. General statistical explanation: a narrower interval indicates greater precision, while a wider interval indicates more uncertainty about the estimated comparison. An interval is not a guarantee that the true effect lies within its bounds, and it does not show the distribution of individual participant outcomes.

For the unadjusted Week 52 risk difference, the estimate for belimumab 1 mg/kg versus placebo is 0.071, with a 95% confidence interval from -0.009 to 0.152. The interval includes zero, so the data are compatible with no difference as well as with differences in either direction across the interval. For belimumab 10 mg/kg versus placebo, the recalculated estimate is 0.098, with a 95% confidence interval from 0.017 to 0.179; that interval lies above zero.

The sponsor’s logistic-regression results use odds ratios instead. The reported 95% confidence interval is 1.08 to 2.19 for 10 mg/kg versus placebo and 0.95 to 1.94 for 1 mg/kg versus placebo. These intervals should be interpreted on the odds-ratio scale, not as absolute percentage-point differences. The 1 mg/kg interval includes 1, the null value for an odds ratio; the 10 mg/kg interval does not.

Precision is limited by the information in the trial and by the analysis method. The registry record does not report confidence intervals for every secondary outcome, the covariates in the sponsor’s models, or details needed to assess all sources of uncertainty. The intervals describe sampling uncertainty under their respective methods; they do not address bias from missing data, outcome definition, or other design and conduct issues.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on the observed effect, not the sample-size assumptions used to design the trial. For these binary outcomes, the figures give participants per arm, not a total across arms or a count of events. The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario targets a stated fraction of the observed effect.

The 80% power column describes the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions. The 90% power column gives the corresponding planning estimate for a 90% chance. These are planning probabilities under an assumed effect and statistical model; they do not describe the probability that the observed trial result is correct.

Each scenario uses a different effect size: the full observed effect, 75% of the observed effect, or 50% of the observed effect. The smaller the effect targeted for detection, the more participants are needed under the same assumptions. The figures are sensitive to the observed effect used as their starting point, so they are not a substitute for a prospective design calculation based on prespecified assumptions.

The plotted planning curve should be read as a visual representation of how the estimated participant requirement changes as the target effect changes. The registry record does not report the original sample-size justification, the effect assumed when the trial was designed, or the trial’s original power calculation. These planning figures are not observed power; observed power is not an appropriate retrospective measure of how conclusive a result is.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.335; treatment proportion p₁ = 0.406; average p̄ = 0.370.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6829 = 1.3384.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6810 = 0.5732.
4. n = (1.3384 + 0.5732)² / (0.0714)² = 717.6, rounded up to 718 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.334545454545455                          # control proportion
p1 <- 0.40590405904059                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(410384)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 718 (80% power), 961 (90% power)
 75% of observed effect: n per arm = 1,264 (80% power), 1,692 (90% power)
 50% of observed effect: n per arm = 2,813 (80% power), 3,766 (90% power)
power.prop.test: 717.6 
Simulated power at n = 718 per arm: 0.797 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s own Week 52 analyses compare each belimumab dose with placebo using logistic regression and report odds ratios with 95% confidence intervals and p-values. For 10 mg/kg, the sponsor reports an odds ratio of 1.54, a 95% confidence interval from 1.08 to 2.19, and p=0.017. For 1 mg/kg, the reported odds ratio is 1.36, a 95% confidence interval from 0.95 to 1.94, and p=0.089.

The recalculations are unadjusted comparisons of the posted response proportions, expressed as risk differences. They yield a risk difference of 0.098 for 10 mg/kg and 0.071 for 1 mg/kg. The sponsor’s odds ratios and the recalculated risk differences are different measures, and the sponsor’s logistic regression may also reflect model choices not described in the registry record. The full adjustment specification is not reported in the registry record.

A discrepancy is flagged between the posted summaries and the recalculations. In that situation, the sponsor’s own analysis takes precedence for describing the trial’s reported statistical result. Recalculation remains useful as a transparent, unadjusted reading of the group summaries, but it should not be presented as the sponsor’s inferential analysis or used to overrule it.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study assesses several outcomes, time points, treatment comparisons, or statistical tests. General statistical explanation: each additional test creates another opportunity for a result to appear unusual by chance. A prespecified strategy may control the overall false-positive risk, for example by defining a testing order or adjusting the significance criterion. The registry record does not report whether such a strategy was used for this trial.

The record lists a primary outcome and several secondary outcomes, with assessments at different weeks and comparisons of two belimumab doses against placebo. It also reports multiple analyses. The formal statistical analysis plan, the prespecified testing hierarchy, and any multiplicity adjustment are not reported in the registry record. Therefore, the secondary p-values should be read as individual results rather than as evidence that a family-wide error rate was controlled.

The primary analysis used a modified intention-to-treat population comprising randomized participants who received at least one dose. The registry classified participants requiring rescue SLE medication, those who dropped out, and those missing Week 52 data as nonresponders. This rule is stated for the primary endpoint, but counts in each category, reasons for missingness, and the treatment of missing data in secondary analyses are not reported in the registry record.

Other details that would help evaluate robustness are not reported in the registry record, including the full analysis population for each secondary outcome, the model covariates, sensitivity analyses, and whether any interim analyses were conducted. These absences limit assessment of how analysis choices may affect the results. They do not change the posted estimates, but they constrain how confidently the results can be generalized beyond the specified analysis rules.

16. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (1.8%), lupus nephritis (1.8%), anaemia (1.5%), pyrexia (1.5%), non-cardiac chest pain (1.5%).

The registry lists serious adverse events affecting 54 participants in the placebo group, 63 in the belimumab 1 mg/kg group, and 61 in the belimumab 10 mg/kg group. Other adverse events are listed for 213, 217, and 219 participants in those respective groups. These are group-specific affected-participant counts; they should not be interpreted as counts of all event episodes.

The listed serious adverse-event terms include pneumonia and lupus nephritis at 1.8% each, anaemia and pyrexia at 1.5% each, non-cardiac chest pain at 1.5%, and abdominal pain at 1.1%. These terms describe events reported in the registry and are not, by themselves, an overall assessment of comparative safety. The record does not provide a causal attribution for each event in this summary.

Death counts are not reported in the registry record. Additional detail about event timing, duration, severity beyond the serious classification, or statistical comparisons is not reported in the registry record. Raw counts alone do not account for follow-up time or establish whether group differences are meaningful. The safety figures should therefore be read as descriptive registry counts, not as a complete safety analysis.

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

The Week 52 results describe how often participants met a specific composite SRI response definition in each study group. The posted response proportions are higher for both belimumab doses than for placebo. The registry’s logistic-regression analysis reports an odds ratio above 1 for each dose comparison, with different degrees of precision. Because the discrepancy flag is true, the sponsor’s own regression analysis takes precedence over the unadjusted recalculation.

The endpoint does not measure every dimension of SLE or capture the full experience of each participant. It combines a threshold change in SELENA SLEDAI with requirements limiting worsening in PGA and BILAG. A participant who improved in one component but did not satisfy the full composite definition would not be classified as a responder. Participants who required rescue medication, dropped out, or lacked Week 52 data were also classified as nonresponders under the stated rule.

The results do not establish the size of benefit for every individual, the effect on outcomes not included in the endpoint, or the long-term course beyond the reported follow-up. They also do not resolve how the findings would change under different missing-data assumptions or outcome definitions. The registry record does not report enough detail to assess all such alternatives.

Statistical evidence and clinical importance are related but distinct. General statistical explanation: an estimate and its confidence interval describe the magnitude and uncertainty of a group comparison, while judgments about importance depend on clinical context and values not captured by a p-value alone. The registry record does not specify a threshold for a clinically important difference. These results should therefore be interpreted as evidence about the stated endpoint and study population, not as a complete account of treatment effects or a recommendation for care.

18. Why This Trial Matters Statistically

This trial illustrates why the endpoint definition and analysis population matter in clinical biostatistics. The primary outcome is not simply a change in one disease-activity score; it combines improvement in SELENA SLEDAI with restrictions on worsening in PGA and BILAG. The classification also incorporates the registry’s rule that rescue medication, dropout, or missing Week 52 data results in nonresponse. Those choices are central to understanding what the response rate represents.

It also demonstrates the importance of distinguishing measures of effect. The recalculated risk differences describe absolute differences in response proportions, while the sponsor reports odds ratios from logistic regression. These quantities answer related but nonidentical questions and cannot be substituted for one another. When a discrepancy is flagged, the sponsor’s reported analysis remains the primary reference, while the unadjusted calculation provides a separate descriptive perspective on the posted summaries.

Finally, the registry highlights how uncertainty and multiplicity shape interpretation. Confidence intervals communicate the range of estimates compatible with each method, and secondary outcomes provide context across different measures and time points. But a large set of outcomes can complicate interpretation when the testing strategy and missing-data procedures are not reported. Planning illustrations based on observed effects can help readers understand how assumed effect size affects participant requirements, but they do not recover the original trial design assumptions.

19. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record does not report the full eligibility criteria, participant characteristics, or the original sample-size justification. Although the study is described as randomized, double-blind, and placebo-controlled, details of sequence generation, allocation concealment, and the success of masking are not reported in the registry record.

The sponsor’s logistic-regression results are reported, but the full model specification and covariates are not reported in the registry record. A discrepancy is flagged between those results and the unadjusted recalculations. The sponsor’s analysis takes precedence, but the missing model detail limits independent assessment of why the estimates differ.

For the primary endpoint, the registry specifies a nonresponder rule for rescue medication, dropout, and missing Week 52 data. The number of participants affected by each circumstance, reasons for withdrawal, and sensitivity analyses are not reported in the registry record. It is therefore not possible to judge from this record alone how robust the result is to alternative missing-data assumptions.

The formal multiplicity plan is not reported in the registry record, despite several secondary outcomes and comparisons. Results for the listed SF-36 and prednisone-reduction outcomes are not reported in the registry record. Safety reporting is also limited in the information available: death counts are not reported in the registry record, and further details about timing and event-level patterns are not given. These limits call for caution when interpreting secondary and safety findings alongside the primary result.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of Belimumab in Subjects With Systemic Lupus Erythematosus — NCT00410384.
• Registry record last updated 2017-02-01; status last verified 2016-12.
• Results first posted 2011-05-05.
• 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.

23. Record Summary

This completed Phase 3 study compared belimumab 1 mg/kg and 10 mg/kg with placebo in participants with active, autoantibody-positive SLE receiving standard therapy. The randomized, double-blind, parallel-group study had a planned duration of 76 weeks and listed enrollment of 819. The primary endpoint was the Week 52 SRI response rate in a modified intention-to-treat population.

Week 52 response proportions were 33.5% for placebo, 40.6% for belimumab 1 mg/kg, and 43.2% for belimumab 10 mg/kg. The registry’s logistic-regression analyses reported odds ratios of 1.36 and 1.54 for the respective dose comparisons. The unadjusted recalculations use risk differences and differ from the sponsor’s reported analyses; the sponsor’s own analysis takes precedence. Important details about multiplicity, model specification, missing-data sensitivity analyses, and the original sample-size design are not reported in the registry record.