A Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases (NCT01012323), a na phase 3 study. The primary outcome is Number of Serious Bacterial Infections Per Person-year of Treatment.

2. Clinical Question

The registry describes an evaluation of NewGam’s efficacy in preventing serious bacterial infections, alongside pharmacokinetic, safety, and quality-of-life assessments. The primary endpoint was an event rate rather than a simple proportion: it related the total number of qualifying serious bacterial infections to patient-years on NewGam treatment. This framing accounts for participants’ time receiving treatment in the denominator.

The registry definition of a serious bacterial infection included bacteraemia or sepsis, bacterial meningitis, osteomyelitis or septic arthritis, bacterial pneumonia, and visceral abscess. The endpoint therefore concerns a specified set of serious bacterial conditions, not all infections. Total infections and antibody trough concentrations were among the listed secondary outcomes.

The registry record does not report the numerical primary endpoint result, its uncertainty, or a comparison with another treatment or a control group. Consequently, the clinical question can be described from the registered endpoint and study design, but the record does not allow the size or precision of the observed event rate to be assessed.

3. Trial Design

This was a phase 3, single-group study of NewGam in patients with primary immunodeficiency diseases. The registry lists Octapharma as the sponsor, an enrollment of 51, a start date of 2010-01, a primary completion date of 2012-06, and a completed status. Allocation was listed as NA, and masking as none. The record therefore describes a study without a randomized control group and without masking.

Participants received NewGam intravenously at 200-800 mg/kg on one of two schedules: every 3 weeks (17 infusions) or every 4 weeks (13 infusions), for 1 year. The registry does not report how participants were assigned to those schedules, or whether schedule choice followed a prespecified rule. Those details are not reported in the registry record.

The stated purpose was to evaluate serious bacterial infections and the pharmacokinetic profile of NewGam, as well as safety and quality of life. Listed secondary outcomes include IgG trough level concentration, trough concentrations of antibodies against several named pathogens, and total number of infections. There were 19 outcome measures in the record, but the registry lists 0 analyses.

Because the study had a single group, the design can describe outcomes during treatment but does not create a randomized estimate of how those outcomes would differ under another treatment or under no treatment. The registry record does not report a statistical analysis plan, a sample-size justification, or details of any interim analyses. No specific reason for the enrollment target or the two dosing schedules can be inferred from the 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set: All participants who received at least 1 complete treatment with NewGam and for whom data on infections were available from at least 1 post-treatment diary entry.

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: Total set: All enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Number of Serious Bacterial Infections Per Person-year of Treatment, measured over Baseline to end of the study (up to 12 months).

The primary endpoint was the number of serious bacterial infections per person-year of treatment, measured from baseline to the end of the study, up to 12 months. The registry defines the rate as the total number of serious bacterial infections divided by patient-years on NewGam treatment. The qualifying infections were bacteraemia or sepsis, bacterial meningitis, osteomyelitis or septic arthritis, bacterial pneumonia, and visceral abscess.

An event rate uses exposure time in its denominator. In general, this can be useful when participants contribute different amounts of time under observation or treatment: the result expresses events relative to time at risk rather than only stating how many participants experienced an event. It does not, by itself, show how events were distributed across participants, when they occurred, or whether any participant experienced more than one event.

The full analysis set was defined as participants who received at least 1 complete treatment with NewGam and had infection data available from at least 1 post-treatment diary entry. The registry record does not report the numerical event rate, the total number of qualifying infections, patient-years of treatment, or an uncertainty interval. It is therefore not possible from this record to assess the observed rate’s magnitude or precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is an event rate. In general, an event rate divides the number of events by a measure of time at risk or exposure. In this study, the registry specified total serious bacterial infections divided by patient-years on NewGam treatment. This differs from a proportion, which would describe the share of participants who experienced at least one event without incorporating each participant’s exposure time into the denominator.

Exposure-based rates can be useful when follow-up time differs among participants. In general, the denominator makes the amount of observed time explicit, so a rate can describe event occurrence relative to time receiving treatment. The rate does not reveal the full pattern of events: it does not say whether events were concentrated in a small number of participants, whether events recurred, or when events occurred. Those details require additional data and analyses. The registry record does not report the total event count or patient-years used for this endpoint.

Counts of events are often analyzed with statistical models designed for count data. In general, a Poisson model is one possible approach when events are related to exposure time. Such a model commonly uses exposure time to account for unequal observation. This is a general explanation, not a claim about the analysis used in this study: the statistical methods are not reported in the registry record.

In general, count data can be over-dispersed when their variability is greater than a simple Poisson model expects. This can occur, for example, when event counts vary substantially between participants or when events cluster. If over-dispersion is present but not accommodated, uncertainty estimates from a model may be too narrow. The registry record does not report a dispersion estimate, a model, or how over-dispersion was assessed or handled. No particular distribution or adjustment can be attributed to this study from the available record.

A confidence interval is a way to express the statistical uncertainty around an estimated effect or rate. In general, a narrower interval indicates greater precision under the model and assumptions used; it does not address every source of bias. The registry record does not report a confidence interval for the primary endpoint, and no interval can be reconstructed without the endpoint result and relevant analysis details. A p-value, if reported, would address compatibility with a specified null hypothesis under an analysis model; it would not describe the clinical importance of an effect. No primary endpoint p-value is reported in the registry record.

The outcome’s analysis population was the full analysis set, defined by treatment receipt and diary availability. This definition excludes participants without at least 1 complete treatment or without infection data from at least 1 post-treatment diary entry. The number in that set, and the reasons any enrolled participants might not meet its criteria, are not reported in the registry record. The record also does not describe imputation, other missing-data procedures, or sensitivity analyses. The endpoint definition therefore identifies who was eligible for the analysis, but it does not show how incomplete observations were handled.

There were 19 outcome measures and 0 analyses listed in the registry record. Multiple outcome measures raise a general statistical issue: when many hypotheses are tested, the chance of at least one apparently notable result can increase. Common approaches include prespecifying a primary outcome, adjusting for multiple testing, or treating secondary findings as exploratory. The registry record does not report a multiplicity procedure or enough analysis detail to determine how the listed outcomes were evaluated. The existence of several registered outcomes should not be read as evidence that each had a reported statistical test.

Planning calculations are distinct from observed results. In general, a sample-size calculation uses assumptions about an effect, variability, significance level, allocation, and desired power to illustrate a design’s requirements. The planning assumptions associated with this record specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions describe a planning illustration, not the original single-group design. Any sample-size result is a planning illustration, not observed power, and cannot substitute for a reported endpoint estimate. The registry record does not report the trial’s own sample-size justification.

Finally, a rate estimate from a single group is descriptive unless interpreted with a suitable comparison or a justified external reference. A comparison with a historical rate would require information about the reference population, outcome definitions, exposure measurement, and relevant differences in care or follow-up. Those details are not reported in the registry record. The design and available results therefore do not support a causal comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 19 outcome measures, including the primary serious bacterial infection rate and secondary measures such as total infections and antibody trough concentrations. It lists 0 analyses. The record does not report a statistical analysis plan, a hierarchy among secondary outcomes, or a method for controlling multiplicity. In general, evaluating multiple outcomes can increase the chance of a chance finding if many tests are performed. Since analyses are not reported, the record does not establish which outcomes were tested or how any multiplicity issue was addressed.

The primary endpoint population was the full analysis set: participants who received at least 1 complete treatment with NewGam and had infection data available from at least 1 post-treatment diary entry. The record does not report the size of that analysis set or how many enrolled participants failed to meet its criteria. It also does not describe missing-data handling, diary completion, imputation, or sensitivity analyses. Thus, the endpoint population is defined, but the consequences of missing or unavailable infection data cannot be assessed.

The enrolled population and the analysis population should not be assumed to be identical. The registry reports enrollment of 51, while the full analysis set has additional eligibility requirements. No analysis-population count is reported in the registry record. Interpretation of the primary endpoint would also depend on the available treatment exposure, which is not reported. These omissions limit assessment of both the analysis coverage and the uncertainty of the endpoint estimate.

11. 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: gout (2.0%), pneumonia (2.0%), bronchiectasis (2.0%), bronchospasm (2.0%), septoplasty (2.0%).

The registry safety record lists 5 participants with serious adverse events among 51 at risk, and 45 participants with other adverse events among 51 at risk. These are counts for the NewGam group. The record does not report deaths as a numerical count, so a death count should not be inferred.

The serious adverse-event terms listed were gout, pneumonia, bronchiectasis, bronchospasm, septoplasty, and thrombocytopenia, each reported as 2.0%. These percentages are registry entries for the terms; the record does not provide event-level detail, timing, severity beyond the serious-event listing, or attribution to treatment. The terms do not establish that NewGam caused the events.

Because this was a single-group study without a concurrent control, these safety data describe events recorded in the study group but do not quantify a treatment-attributable increase or decrease in risk. The record does not report how participants could contribute to more than one event term, so the listed terms should not be added together or treated as distinct participants. The counts also do not provide exposure-adjusted safety rates.

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

The study record describes a phase 3 evaluation of NewGam in patients with primary immunodeficiency diseases. Its primary endpoint was defined as serious bacterial infections per person-year of treatment, using a specified set of serious bacterial conditions. The registry also lists pharmacokinetic, infection, safety, and quality-of-life aims. This information clarifies what the study set out to assess.

The record does not report the numerical primary endpoint result, its uncertainty, or a comparison with another group. It therefore does not establish how frequent serious bacterial infections were during treatment or how precisely that frequency was estimated. The registry’s outcome definitions and study purpose cannot substitute for those missing results.

The design also limits what can be concluded about causation. With one group and no randomized comparator, outcomes recorded during treatment cannot by themselves show what would have happened under a different treatment or without treatment. The study’s completed status does not supply a comparative estimate. Nor do the listed secondary outcomes establish their results when analyses and numerical outcome values are not reported in the registry record.

The safety counts are descriptive. They report participants with serious and other adverse events, but do not establish that NewGam caused those events or that the event frequency differs from another treatment. The listed serious-event terms provide additional descriptions, not a controlled safety comparison.

Accordingly, the registry record supports an account of the study design, endpoint definitions, analysis-population criteria, and recorded safety counts. It does not support a conclusion about the size or precision of the primary endpoint effect, a comparative benefit or harm, or a causal effect of treatment. Those questions require outcome estimates and analysis details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This study illustrates why the definition of an endpoint matters for interpretation. The primary outcome was not simply whether participants experienced an infection; it was an event rate with patient-years on treatment as the denominator. That choice makes exposure time part of the estimand and signals that the number of events must be interpreted in relation to time receiving treatment.

The case also shows the limits of an event-rate definition when the numerical result and denominator are not reported. Without the event count, exposure time, and rate estimate, readers cannot assess the observed frequency or its precision. A clearly described endpoint is valuable, but it cannot replace the result itself.

Study design is equally central. The single-group structure permits descriptive assessment during treatment, but lacks a randomized concurrent comparison. This distinction prevents a descriptive rate from being mistaken for a treatment effect. Statistical interpretation depends not only on the endpoint and calculations, but also on what comparisons the design can support.

The record’s analysis-population definition further highlights the importance of understanding who contributes to an endpoint. Treatment receipt and diary availability were eligibility conditions for the full analysis set, yet the number meeting those conditions and the handling of missing information are not reported. An enrollment count alone does not answer how many participants contributed to the primary analysis.

Finally, safety counts and multiple registered outcomes require careful reading. Descriptive adverse-event counts do not establish causation, while a list of outcomes does not show that each was analyzed or how multiplicity was handled. These distinctions are broadly relevant when interpreting registry records: endpoint definitions, analysis populations, comparison groups, missingness, and uncertainty all shape what conclusions the statistics can support.

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 main limitation for interpreting the primary endpoint is that its numerical result is not reported in the registry record. The event count, treatment exposure in patient-years, rate estimate, and uncertainty interval are also not reported. Without these quantities, the observed rate and its precision cannot be assessed.

The design was single-group, with allocation listed as NA and masking listed as none. There was no concurrent randomized comparator. The registry record therefore does not provide a basis for a randomized treatment comparison, and treatment effects cannot be separated from other influences on outcomes using the study design alone.

The primary analysis population required at least 1 complete treatment and infection data from at least 1 post-treatment diary entry. The number meeting those criteria is not reported. The record also does not describe missing-data procedures, diary completeness, or sensitivity analyses. This leaves uncertainty about analysis coverage and the effect of unavailable infection observations.

The two infusion schedules are described, but the registry does not report how participants followed each schedule or how their treatment exposure was distributed. Such information would be relevant to understanding the person-year denominator and interpreting an exposure-based event rate. No numerical schedule-specific endpoint results are reported in the registry record.

The record lists 19 outcome measures and 0 analyses, and does not report a statistical analysis plan, multiplicity approach, model, or dispersion assessment. Consequently, the exact analysis methods and the treatment of multiple outcomes cannot be evaluated. The safety record provides descriptive counts but does not report a comparative assessment or deaths count. These limitations are specific to what the registry record documents and do not establish whether additional information exists elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of NewGam, Human Immunoglobulin 10%, in Patients With Primary Immunodeficiency Diseases — NCT01012323.
• Registry record last updated 2017-03-16; status last verified 2017-02.
• Results first posted 2017-03-16.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The registry describes a completed phase 3, single-group study of NewGam in patients with primary immunodeficiency diseases. Enrollment was 51. The study started in 2010-01 and had primary completion in 2012-06. Participants received intravenous NewGam at 200-800 mg/kg every 3 weeks (17 infusions) or every 4 weeks (13 infusions) for 1 year. Allocation was listed as NA and masking as none.

The primary endpoint was serious bacterial infections per person-year of treatment, from baseline to the end of the study, up to 12 months. The full analysis set required at least 1 complete treatment and infection data from at least 1 post-treatment diary entry. The numerical primary endpoint result and its uncertainty are not reported in the registry record. The record lists 19 outcome measures and 0 analyses.

The safety record lists 5 participants with serious adverse events and 45 with other adverse events among 51 at risk. These descriptive figures do not establish treatment causation or provide a controlled comparison.