High Infusion Rate Study of Immunoglobulin Intravenous (Human) 10% (NewGam): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for High Infusion Rate Study of Immunoglobulin Intravenous (Human) 10% (NewGam) (NCT01313507), a na phase 3 study. The primary outcome is Percentage of Participants Who Experienced at Least 1 Adverse Event Causally Related to the Administration of the Study Drug.

2. Clinical Question

The study asked whether high infusion rates of intravenous NewGam could be administered with acceptable safety and tolerability in participants with primary immunodeficiency disease. Its primary question focused on the percentage of participants who experienced at least one adverse event judged by the investigator to be possibly or probably related to study-drug administration during follow-up.

The registry record does not report the primary endpoint count or percentage. It therefore does not provide a numerical answer to the main safety question. The reported counts for serious and other adverse events describe safety findings, but they do not establish how many participants met the primary endpoint’s specific causality definition.

3. Trial Design

This was a prospective, open-label, non-controlled, non-randomized, multicenter Phase III study. It is described as an extension of NGAM-01. The registry record gives the study start as 2011-05, primary completion as 2012-09, and status as completed. Enrollment was 21.

All participants received NewGam. Their infusion interval continued from the main study: every 3 weeks or every 4 weeks. The registry describes a treatment period of 3 months, with 5 or 4 total infusions, respectively. The reported dose range was 200-800 mg/kg intravenously. The record does not give the number of participants assigned to each interval or outcomes broken down by interval.

Because there was no control group and no random allocation, the study cannot provide a randomized comparison of the two schedules or a treatment-versus-control effect. Any differences between participants following the different intervals could reflect their prior treatment schedule or other participant characteristics; the registry record does not describe an analysis designed to separate such explanations.

Open-label means participants and investigators were not masked to treatment. In general, knowledge of treatment can influence the reporting or assessment of subjective outcomes. The primary endpoint included investigator judgment about whether an adverse event was possibly or probably related to the study drug, so the open-label design is relevant when interpreting that judgment. The registry record does not report procedures to reduce or assess this potential influence.

The primary endpoint follow-up ran from the NGAM-01 follow-up visit at baseline to the NGAM-05 follow-up visit at the end of the study, up to 4 months. A secondary outcome was change from baseline in quality of life at the end of the study. The registry record does not report the result of that secondary outcome or additional details of its measurement.

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

Analysis population for the primary outcome, as defined in the registry: Safety analysis set: All participants who received at least 1 dose of NewGam.

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: Safety analysis set: All participants who received at least 1 dose of NewGam.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Experienced at Least 1 Adverse Event Causally Related to the Administration of the Study Drug, measured over Baseline (follow-up visit of study NGAM-01) to the end of the study (follow-up visit of study NGAM-05) (up to 4 months).

The primary endpoint is the percentage of participants who experienced at least one adverse event causally related to administration of NewGam. For this endpoint, the record defines causal relation as an investigator assessment that the event was probably or possibly related to study drug. The timeframe was from the baseline follow-up visit of NGAM-01 through the end-of-study follow-up visit of NGAM-05, up to 4 months.

This type of endpoint is used to describe how many participants in the treated group experienced a safety event meeting a specified definition during follow-up. Counting participants with at least one qualifying event gives a participant-level summary: repeated qualifying events in the same participant would not make that person count as multiple participants for this endpoint. The registry record does not provide the actual number or percentage meeting the definition, so the endpoint’s observed result cannot be described numerically.

The definition is narrower than a count of all adverse events. It requires an event and an investigator’s assessment of possible or probable relation to the study drug. The serious and other adverse-event counts reported separately do not, by themselves, show how many events met that causality criterion. Nor does the endpoint measure comparative risk, because the study had no control group.

In general, a safety endpoint of this kind helps characterize events observed during treatment and follow-up. It does not by itself establish that the study drug caused an event; causality assessment in this record was based on investigator judgment. The registry record does not report a confidence interval or another measure of precision for the primary endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a participant-level percentage as the primary outcome, but does not post the result or a statistical analysis for that endpoint. The following concepts explain how this kind of outcome is generally interpreted; they do not add unreported analyses to this study.

What does a participant-level percentage represent?

For a binary safety outcome, each participant is classified according to whether the defined event occurred at least once during the stated observation period. The percentage is the share of the relevant analysis population meeting that definition. This differs from counting every event: a participant with repeated events still contributes one participant to a measure defined as having at least one event.

Here, the endpoint definition also includes an investigator assessment of causality. An adverse event qualifies only if the investigator judges it possibly or probably related to study-drug administration. The posted safety summary separates serious adverse events from other adverse events, but does not give a cross-classification by the endpoint’s causality assessment. Therefore, those safety counts cannot be used to reconstruct the primary endpoint.

What does a confidence interval add?

In general, a confidence interval expresses the statistical uncertainty around an estimated quantity. For a participant-level percentage, it helps convey how much the observed result could vary because the study includes a finite group of participants. A point estimate alone does not show that uncertainty. The registry record does not report a confidence interval for the primary endpoint, and the endpoint result itself is not reported.

A confidence interval would not correct limitations in the design. In a single-group study, it can describe uncertainty around the observed group’s outcome under a statistical model, but it cannot create a control group or remove confounding. It also cannot resolve uncertainty in investigator causality judgments.

Why does the design matter for analysis?

This study had one treatment group and no randomization. The two infusion intervals reflect participants continuing their interval from the main study, not a randomized assignment between schedules. In general, a direct causal comparison requires a design and analysis that support comparison between treatment groups. A single-group percentage is descriptive and does not estimate a relative treatment effect against a control.

The open-label design is also pertinent to a judgment-based safety outcome. In general, knowledge of treatment may affect whether an event is reported or how its relation to treatment is assessed. The registry record does not report masking, independent adjudication, or another procedure that would address this concern. The record identifies the study as unmasked.

What is the analysis population?

The primary endpoint description names the safety analysis set, defined as all participants who received at least one dose of NewGam. This defines who is intended to contribute to that endpoint. The adverse-event summary reports 21 participants at risk in the NewGam group. The primary endpoint’s analyzed count and denominator are not reported in the registry record, so the safety-set definition should not be mistaken for a posted primary result.

In general, a clear analysis population matters because exclusions or missing observations can change which participants contribute to an estimate. The registry record does not explain how missing primary endpoint information was handled, whether all enrolled participants received a dose, or whether the analysis population differed from enrollment.

What can planning calculations tell a reader?

In general, sample-size planning calculations describe the number of participants that might be needed under stated assumptions about the effect to detect, the significance level, allocation, and statistical model. They are not results from the trial. Calculations based on an observed effect are planning illustrations rather than the trial’s original design justification, and they do not represent observed power. The registry record does not report the original sample-size justification.

For a single-group safety endpoint, the design goal and assumptions would need to match the outcome and estimand being studied. A calculation for a two-arm comparison does not turn this non-controlled study into a comparative trial. No trial-specific statistical analysis plan, model, confidence interval method, or hypothesis test for the primary endpoint is reported in the registry record.

In general, over-dispersion refers to more variability in data than a statistical model assumes. It can affect standard errors and intervals in settings where the chosen model is sensitive to that assumption. It is not possible to assess over-dispersion from the endpoint description alone, and the registry record does not report an analysis of it.

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("NewGam")
n      <- c(21)
events <- c(4)
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  NewGam  21  4  19.0  5.4  41.9  7.7  40.0  7.8  40.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists three outcome measures and no analysis entries. It identifies the primary safety outcome and one secondary outcome, change from baseline in quality of life at the end of the study. The record does not give results for the primary endpoint or the quality-of-life outcome. It does not describe a statistical analysis plan for the listed outcomes.

Multiplicity arises in general when several outcomes, time points, subgroups, or statistical tests are examined. If many tests are interpreted together, the chance of at least one apparently notable result can increase. Statistical plans may address this through prespecified outcome hierarchies or adjustments, but no multiplicity strategy is reported in the registry record. There is no posted set of analyses from which to assess how multiple testing was handled.

The primary endpoint population is defined as the safety analysis set, consisting of participants who received at least one dose of NewGam. The adverse-event summary gives 21 participants at risk. The record does not state how missing primary endpoint data were handled, whether any endpoint observations were missing, or whether imputation or another missing-data method was used. These details should be treated as not reported in the registry record, rather than assumed to involve complete data or a particular method.

The record also does not describe a separate analysis population for the secondary quality-of-life outcome. No inference should be made about whether participants with incomplete quality-of-life observations were excluded, included by a specified method, or otherwise handled. The posted information supports describing the named safety population and the listed outcomes, but not reconstructing unreported analysis decisions.

12. 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 non-serious adverse event terms

The registry safety summary reports 0 participants with a serious adverse event among 21 at risk in the NewGam group. It reports 12 participants with other adverse events among 21 at risk. These figures count participants affected, not necessarily the total number of events. They are descriptive observations for this group and do not provide a comparison with an untreated or alternative-treatment group.

Serious adverse events and other adverse events are distinct categories in the registry summary. The counts should not be combined with the primary endpoint unless the relevant event-level and causality information is available. The primary endpoint requires at least one event judged possibly or probably related to study-drug administration; the registry record does not report how many participants met that definition.

The number of deaths is not reported in the registry record. The serious-event terms are not reported in the registry record. Neither missing detail should be read as evidence that there were no deaths or no particular serious-event types. In general, a zero observed count in a limited study population describes what was recorded among those participants, not certainty about what could occur elsewhere.

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

The posted record establishes that 21 participants enrolled in a prospective, open-label, single-group extension study of NewGam for primary immunodeficiency disease. It describes two infusion intervals continued from the main study and gives a primary safety endpoint based on investigator-assessed possible or probable relation to study drug. It also reports the counts of participants affected by serious and other adverse events.

The record does not report the primary endpoint’s number or percentage. It therefore does not show how often participants experienced an adverse event meeting the endpoint’s causality definition. The serious and other adverse-event counts provide separate descriptive information, but they cannot fill that gap. No estimate of precision for the primary endpoint is reported.

The study design does not support a randomized comparison of infusion intervals or a comparison with a control treatment. The data describe observations among participants receiving NewGam under the study conditions. They do not establish what would have happened to the same participants under another schedule or without NewGam. The open-label design and investigator-assessed causality are relevant when interpreting safety observations.

In general, a trial result is most informative when its outcome definition, analysis population, estimate, uncertainty, and design are all considered together. Here, the outcome definition and safety population are described, but the primary estimate, missing-data approach, and statistical analysis are not reported in the registry record. Conclusions should therefore remain limited to the study design and the posted safety counts, without implying a treatment effect or a comparative safety result.

14. Why This Trial Matters Statistically

This trial illustrates an important distinction between a safety outcome being defined and its result being reported. The registry record specifies a participant-level endpoint tied to investigator judgments of possible or probable causality, but does not provide the count or percentage of participants meeting that definition. Without the estimate, readers cannot assess the endpoint’s observed frequency or its precision.

It also demonstrates why study design determines the kinds of statistical conclusions that are available. A prospective, single-group study can describe events observed during treatment and follow-up. Without randomization or a control group, it cannot estimate a treatment-versus-control difference, and continuation of different prior infusion intervals does not create a randomized schedule comparison.

The safety summary further shows why outcome definitions must not be conflated. Counts of serious and other adverse events are not interchangeable with an endpoint that requires a specified investigator assessment of drug relation. A numerical count can be accurate for its own category while still not answering the primary question.

Finally, statistical interpretation depends on more than a sample size or an event count. The analysis population, handling of missing observations, uncertainty estimates, and analysis plan all shape how results can be understood. Several of these details are not reported in the registry record. Recognizing those boundaries is part of evaluating clinical evidence: it prevents descriptive observations from being mistaken for comparative effects or for a complete statistical analysis.

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.

The most important limitation for interpreting the primary outcome is that its result is not reported in the registry record. The endpoint definition and timeframe are available, but no count, percentage, confidence interval, or analysis is posted. The reported serious and other adverse-event figures cannot substitute for this causality-defined outcome.

The study was non-controlled and non-randomized, and all participants received NewGam. Therefore, the record does not support a causal comparison against a control group. The two infusion intervals followed participants’ prior schedules; the registry does not give group sizes or interval-specific outcomes. A schedule comparison cannot be reconstructed from the overall safety counts.

The study was open-label, and the primary endpoint used investigator assessment of event relatedness. The record does not report independent adjudication or other procedures addressing possible influence on reporting and assessment. It also does not describe the handling of missing data, an analysis plan, a multiplicity strategy, or the original sample-size justification.

Enrollment was 21, which limits the amount of participant-level information available for describing uncommon outcomes. In general, estimates based on limited observations can be imprecise; however, no precision estimate for the primary endpoint is posted, so its uncertainty cannot be quantified from the registry record. The death count and serious-event terms are also not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: High Infusion Rate Study of Immunoglobulin Intravenous (Human) 10% (NewGam) — NCT01313507.
• Registry record last updated 2017-03-29; status last verified 2017-02.
• Results first posted 2017-03-29.
• 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

NCT01313507 is a completed, prospective, open-label, non-controlled, non-randomized, multicenter Phase III extension study of intravenous NewGam in participants with primary immunodeficiency disease. Enrollment was 21. Participants continued an infusion interval of every 3 weeks or every 4 weeks, receiving 200-800 mg/kg for 3 months.

The primary outcome was the percentage of participants with at least one adverse event judged possibly or probably related to study-drug administration, assessed from the NGAM-01 follow-up visit to the NGAM-05 end-of-study visit, up to 4 months. The primary outcome result is not reported in the registry record. The safety summary reports 0 participants with a serious adverse event and 12 with other adverse events among 21 at risk. No control group was included, and the record does not report a comparative analysis, missing-data method, or statistical analysis plan.