Non-Interventional Study on the Tolerability and Efficacy of IVIG: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Non-Interventional Study on the Tolerability and Efficacy of IVIG (NCT02303093), a registered phase not stated study. The primary outcome is Adverse Drug Reactions.

2. Clinical Question

3. Trial Design

This registry record describes a completed non-interventional study titled Non-Interventional Study on the Tolerability and Efficacy of IVIG. Octapharma is listed as the sponsor. The record lists enrollment of 344 and gives a study start date of 2011-08-01 and a primary completion date of 2020-06-05. Its brief summary describes a non-interventional study on the tolerability and efficacy of octagam® 10%.

The listed interventions are Octagam IVIG 5% or 10% and Panzyga. Group descriptions include patients receiving Octagam 5%, patients receiving Octagam 10%, and patients receiving combinations of Octagam and Panzyga. Some groups are identified according to the product being received at the time of the adverse-event observations. These descriptions do not establish that participants were assigned to groups by a common protocol-defined treatment decision or that the groups were comparable at baseline.

The registry record explicitly notes that this is not a randomized comparison and that allocation is not stated. The groups are therefore best understood as descriptive groups in a non-interventional record, rather than as randomized arms designed for a direct treatment contrast. Differences in their reported event counts could reflect differences in the participants, treatment histories, observation, or other factors; the record does not report enough information to separate those possibilities.

The primary endpoint is adverse drug reactions, described as the number of patients with adverse drug reactions over a timeframe of up to one year. Infection occurrence is listed as a secondary outcome. The record lists two outcome measures but does not report an analysis for either one. Details such as eligibility criteria, recruitment methods, treatment-selection rules, follow-up procedures beyond the primary endpoint timeframe, and the statistical analysis plan 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.

Overall Study

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 Adverse Drug Reactions, measured over up to one year.

The stated primary endpoint is Adverse Drug Reactions, measured as the number of participants with adverse drug reactions. Its listed timeframe is up to one year. Counting participants who experience an event is a binary-outcome approach: each participant is classified according to whether the event occurred, and the reported quantity is a count rather than a measure of event severity, duration, or recurrence.

In general, an endpoint based on participants with adverse reactions can provide a direct description of how many people were recorded as affected during the specified observation period. It may be useful for characterizing tolerability because it focuses on people who experienced an event, rather than counting repeated events in the same person as separate participants. That general interpretation depends on clear event definitions, consistent ascertainment, and adequate follow-up. Those operational details are not reported in the registry record.

The posted adverse-event figures distinguish serious events from other events, but the record does not establish that these figures are the primary endpoint results for adverse drug reactions. An adverse event and an adverse drug reaction are not automatically interchangeable descriptions: the record would need to state how events were assessed and attributed to treatment. A separate infection occurrence outcome is listed, but its results are not reported in the registry record. The endpoint definition and timeframe are stated; a primary-endpoint analysis and its uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record identifies a non-interventional study and does not report statistical analyses. The explanations below describe general statistical concepts relevant to interpreting the posted counts; they do not assert that these methods were used in the study.

What does a participant count describe?

For a binary outcome, each person is classified as having or not having the event under the definition used for the analysis. A count of participants with an event describes the observed number meeting that definition. The number at risk gives context for the group in which the count was recorded. A count alone does not quantify uncertainty, establish a causal relationship, or show whether a difference between groups is compatible with chance variation. Those questions require an explicitly defined analysis and, commonly, an interval estimate or hypothesis test.

The posted figures distinguish serious adverse events from other adverse events. These are separate event categories in the registry record. They should not be assumed to be mutually exclusive, or assumed to represent the primary adverse drug reaction endpoint, unless the record explains the definitions and counting rules. It does not report those details. Nor does it report whether a participant with multiple events is counted once or more than once within the event-term listings.

What does a confidence interval mean?

In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified model and analysis procedure. It is not a guarantee that the true value lies within the interval, nor does it address biases caused by selection, measurement, confounding, or incomplete follow-up. The registry record does not report confidence intervals for the primary endpoint or for comparisons between the listed groups. Without an estimate and its uncertainty, the precision of a comparative effect cannot be assessed from these counts alone.

Why does study allocation matter?

Random assignment can help balance measured and unmeasured characteristics between treatment groups on average, supporting a causal interpretation when other design and analysis conditions are met. This record is explicitly not a randomized comparison, and allocation is not stated. Consequently, the group counts do not have the protection against selection differences that random assignment is intended to provide. In a non-interventional study, treatment choice and treatment history may be related to participant characteristics or clinical circumstances. The registry record does not report the information needed to assess those relationships or adjust for them.

Even a statistical adjustment cannot automatically remove confounding. Adjustment depends on having suitable variables measured reliably and on a defensible model. The registry record does not report adjusted estimates, covariates, or a model for comparing groups. No adjusted comparison should be inferred from the descriptive counts.

What is over-dispersion, and is it relevant to these counts?

In general, over-dispersion means that observed variability is greater than a statistical model expects. It can matter for count outcomes when observations are more variable than assumed, because standard errors and uncertainty estimates may then be too small if the model does not account for that extra variation. The primary endpoint is described as a participant count for a binary event, while the posted safety figures are also counts of affected participants. The registry record does not report a model, dispersion assessment, or inferential analysis, so it is not possible to say whether over-dispersion was assessed or relevant to an analysis conducted for this study.

What can be inferred from the listed event percentages?

The record lists Pulmonary embolism at 9.1% and five other serious-event terms at 0.7% each. It does not state the denominator, whether the percentages refer to participants or events, or whether people could contribute to multiple terms. Percentages require a defined numerator and denominator for interpretation. Without that information, the terms and percentages can be quoted as reported, but should not be treated as comparable group-specific risks or as evidence of a treatment effect.

How should planning calculations be understood?

In general, sample-size calculations describe how many participants or events a future design might require under specified assumptions. They are planning illustrations, not observed power and not evidence that a study was designed or analyzed according to those assumptions. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. The stated description specifies that time-to-event planning uses a total number of events and other planning calculations use participants per arm. The registry record does not report its own sample-size justification, and no particular planning estimate or fraction should be interpreted as an observed study result.

Because the study is non-interventional and the record reports no statistical analyses, these general concepts explain what would be needed for inferential claims; they do not turn the posted descriptive counts into a formal comparison. The analytic methods, if any, are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Octagam 5%", "Octagam 10%", "Octagam 5% and Octagam 10%, While Under Octagam 5%", "Octagam 5% and Octagam 10%, While Under Octagam 10", "Octagam 10% and Panzyga, While Under Octagam 10%", "Octagam 10% and Panzyga, While Under Panzyga")
n      <- c(139, 183, 11, 11, 11, 11)
events <- c(17, 37, 0, 1, 9, 9)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Octagam 5%  139  17  12.2  7.3  18.9  7.8  18.7  7.8  18.7
ARM  Octagam 10%  183  37  20.2  14.7  26.8  15.0  26.6  15.0  26.6
ARM  Octagam 5% and Octagam 10%, While Under Octagam 5%  11  0  0.0  0.0  28.5  -0.0  25.9  0.2  26.5
ARM  Octagam 5% and Octagam 10%, While Under Octagam 10  11  1  9.1  0.2  41.3  1.6  37.7  2.1  38.5
ARM  Octagam 10% and Panzyga, While Under Octagam 10%  11  9  81.8  48.2  97.7  52.3  94.9  51.6  94.5
ARM  Octagam 10% and Panzyga, While Under Panzyga  11  9  81.8  48.2  97.7  52.3  94.9  51.6  94.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures: adverse drug reactions as the primary outcome and infection occurrence as a secondary outcome. It reports no statistical analyses. A multiplicity strategy for handling the evaluation of multiple outcomes, event categories, groups, or comparisons is not reported in the registry record. The record also does not report a hierarchy of hypotheses, a correction for multiple testing, or a designation of which analyses were confirmatory versus exploratory.

In general, examining multiple outcomes or making multiple comparisons increases the chance of finding an apparently notable result by chance if each is assessed separately. A prespecified analysis plan can clarify which questions are primary and how uncertainty should be interpreted across them. Since an analysis plan and inferential results are not reported, no conclusion about multiplicity control can be drawn for this study.

Information about missing data is not reported in the registry record. It does not describe how participants with incomplete follow-up, missing outcome assessments, or unknown event status were handled. The number of participants eligible for each endpoint analysis and the analysis populations are also not reported in the registry record. Enrollment of 344 is recorded, but enrollment alone does not establish how many participants contributed data to each outcome or group.

In general, missingness can affect interpretation if participants with unavailable outcome data differ from those whose outcomes are observed. Analyses may address that concern through stated assumptions and methods, but the approach cannot be evaluated without knowing the extent and handling of missing data. The registry record does not report imputation, censoring rules, sensitivity analyses, or a missing-data assumption. These omissions limit assessment of how completely the posted counts represent the participants enrolled and the endpoint timeframe.

12. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pulmonary embolism (9.1%), cardiogenic shock (0.7%), embolism (0.7%), hepatic enzyme increased (0.7%), thrombosis (0.7%).

The serious adverse-event counts are reported separately from counts for other adverse events. In the Octagam 5% group, 3 of 139 participants at risk had a serious adverse event, and 13 of 139 had another adverse event; 1 death is listed. In the Octagam 10% group, the corresponding counts are 1 of 183 for serious events and 37 of 183 for other events, with 0 deaths listed. Each of the four groups involving combinations of products lists 11 participants at risk. Their serious-event counts are 0, 0, 1, and 0, and their other-event counts are 0, 1, 9, and 9, in the order described in the registry record; no deaths are listed for those groups.

The record also lists serious-event terms and percentages: Pulmonary embolism at 9.1%; Cardiogenic shock, Embolism, Hepatic enzyme increased, Thrombosis, and Anaemia at 0.7% each. The denominator and calculation basis for those percentages are not reported in the registry record. These terms should not be assumed to be group-specific or mutually exclusive. The posted counts describe reported events in the listed groups; they do not establish that an event was caused by a product, and the groups are not a randomized, like-for-like comparison.

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

The registry record documents a non-interventional study with enrollment of 344 and lists adverse-event counts across groups receiving Octagam and, in some groups, Panzyga. Those figures give readers descriptive information about the serious and other adverse events recorded in the listed groups. The primary endpoint is identified as the number of participants with adverse drug reactions over up to one year, but no statistical analysis of that endpoint is reported in the registry record.

The record does not establish a causal effect of any treatment. It states that the study is not a randomized comparison, and allocation is not stated. The groups are not described as like-for-like controls; some involve changes or combinations of products. Without randomization or a reported adjustment strategy and supporting participant-level information, differences in counts cannot be attributed to treatment rather than differences in who was observed, treatment history, or other factors.

The record also does not report confidence intervals, hypothesis tests, adjusted estimates, or a comparative effect. Thus, the precision of a treatment contrast cannot be evaluated, and the posted counts should not be read as proof of either benefit or harm relative to another product. The serious-event percentages are listed without a reported denominator or calculation basis, which further limits their interpretation.

In general, non-interventional safety data can describe events observed in practice and can identify patterns for further study. Their interpretation depends on clear event definitions, reliable recording, complete follow-up, and appropriate consideration of differences between participants. The registry record does not report enough methodological detail to assess those features fully. Infection occurrence is listed as a secondary outcome, but its results are not reported in the registry record. The defensible conclusion is therefore limited to describing the posted event counts and terms, while recognizing that comparative efficacy and causal safety conclusions are not established by the reported information.

14. Why This Trial Matters Statistically

This record is statistically informative in part because it illustrates the distinction between descriptive safety reporting and a comparative treatment analysis. Counts of participants with serious and other adverse events are concrete summaries of what was recorded in groups receiving Octagam, sometimes alongside Panzyga. But counts do not, by themselves, answer whether one treatment changes the likelihood of an outcome compared with another.

The design context is essential to interpretation. The registry record describes a non-interventional study, states that it is not a randomized comparison, and says allocation is not stated. Those features mean the groups cannot be assumed comparable. In general, treatment selection in non-interventional research may relate to participant characteristics or prior treatment. A statistical comparison would need a clearly specified question, information on relevant differences, and a defensible analysis. The record does not report such an analysis.

The record also highlights the importance of matching an endpoint definition to the result being interpreted. The stated primary endpoint concerns participants with adverse drug reactions, whereas the posted safety figures distinguish serious adverse events and other adverse events. The relationship between those categories and the primary endpoint is not reported in the registry record. Clear definitions and attribution rules are necessary before interpreting safety counts as results for a particular endpoint.

Finally, the record lists a secondary outcome, infection occurrence, without reporting its results, and it provides no inferential analyses or uncertainty estimates. Those absences constrain what can be concluded, but they do not erase the descriptive value of the recorded safety information. The statistical lesson is to separate what the registry directly reports from what would require an analysis the record does not contain.

15. 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 specific to this study record affect interpretation. The groups are not randomized and are explicitly described as not being a like-for-like control comparison. Allocation is not stated. The group descriptions include treatment combinations, and some identify the product being received when events were counted. These features make direct comparison difficult and prevent the group counts from serving as a simple estimate of relative treatment effects.

The record gives an overall enrollment of 344, but the analysis population for the primary endpoint is not reported in the registry record. The adverse-event groups have their own counts at risk, and the record does not explain how participants moved into or between the treatment descriptions, whether group membership could overlap, or how follow-up was assigned. These details matter when interpreting group denominators and event counts.

The primary endpoint is described as adverse drug reactions, while the posted safety results distinguish serious and other adverse events. The registry record does not report the event definitions, attribution procedures, ascertainment methods, or how the posted safety categories relate to the primary endpoint. The basis for the listed serious-event percentages is also not reported in the registry record.

No statistical analyses are reported. The record provides no confidence intervals, comparative estimates, adjustment methods, multiplicity plan, missing-data procedures, or endpoint-specific analysis populations. Infection occurrence is listed as a secondary outcome, but its results are not reported in the registry record. The record also does not report its own sample-size justification or statistical analysis plan. These limitations mean the available information supports descriptive reading of the posted counts, but does not support an assessment of comparative precision or causal effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Non-Interventional Study on the Tolerability and Efficacy of IVIG — NCT02303093.
• Registry record last updated 2021-06-29; status last verified 2021-06.
• Results first posted 2021-06-29.
• 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.

19. Record Summary

The completed registry record concerns a non-interventional study sponsored by Octapharma, with enrollment of 344. It lists a start date of 2011-08-01 and a primary completion date of 2020-06-05. The study title concerns the tolerability and efficacy of IVIG; the brief summary refers to octagam® 10%.

The stated primary endpoint is the number of participants with adverse drug reactions over up to one year. The listed interventions are Octagam IVIG 5% or 10% and Panzyga. The record lists serious and other adverse-event counts for six treatment descriptions, along with serious-event terms and percentages. Infection occurrence is listed as a secondary outcome, but its results are not reported in the registry record.

The registry record states that this is not a randomized comparison, that allocation is not stated, and that the groups are not a like-for-like control comparison. It reports no statistical analyses. Comparative estimates, uncertainty, missing-data methods, analysis populations, and a multiplicity plan are not reported in the registry record. The posted information is therefore descriptive and does not establish causal treatment effects.