Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease (NCT01614574), a na phase 3 study. The primary outcome is Number of Severe Adverse Events (SAE).

2. Clinical Question

3. Trial Design

This was a Phase 3, multicenter, open-label, single-group study of velaglucerase alfa in Japanese patients with Gaucher disease. The registry reports that the study was completed and lists enrollment as 6. Its recorded start date is 2012-03-02, and its primary completion date is 2013-05-25. These dates describe the registry record; they do not, by themselves, establish when each participant began or completed treatment.

Open-label means the study was not masked: the record lists masking as none. A single-group design means the intervention was evaluated in one treatment group rather than against a concurrent control group. The registry does not describe a random allocation procedure, and it explicitly identifies that there was no randomized comparison. Consequently, comparisons between treatment arms are not applicable, and within-group changes do not have a concurrent control to help separate treatment-associated changes from other influences.

The stated primary objective was to evaluate the safety of every-other-week dosing. The intervention is listed as velaglucerase alfa, and the treatment arm is labelled VPRIV® (15-60 U/kg). The registry does not report additional dosing instructions, the number of infusions, or detailed follow-up procedures. The primary endpoint timeframe is Baseline to week 51.

The registry also lists changes from baseline in hemoglobin concentration, platelet count, liver volume normalized to body weight, spleen volume normalized to body weight, plasma chitotriosidase levels, and CCL18 levels as secondary outcomes. It records 11 outcome measures overall, but the information recorded does not give numerical results for those secondary outcomes. The statistical analysis plan, analysis populations, and reasons for the selected enrollment 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 Number of Severe Adverse Events (SAE), measured over Baseline to week 51.

The primary endpoint is titled “Number of Severe Adverse Events (SAE),” with the unit recorded as events and a timeframe from Baseline to week 51. It is a count outcome: conceptually, it captures how many severe adverse events are recorded during the specified observation period. This type of endpoint is used in safety evaluation because it focuses on serious harms observed during treatment and follow-up, rather than on a change in a laboratory measurement or disease marker.

Counts of events and counts of participants who experience an event are not interchangeable. One participant may experience more than one event, so an event count can differ from the number of affected participants. The registry’s adverse-event summary separately reports participants at risk and participants affected, while the named primary endpoint is expressed in events. The record does not provide the numerical result for the primary endpoint, clarify the operational definition of “severe,” or explain how events were attributed, coded, or adjudicated.

That distinction matters when interpreting the available safety summary. The reported number of participants with a serious adverse event is not automatically the total number of severe adverse events counted by the primary endpoint. Nor does the endpoint title alone establish how severity was defined. Those details, and the primary endpoint result itself, are not reported in the registry record. The endpoint identifies the intended safety measure and observation period, but the available information is insufficient to reconstruct its complete analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a Phase 3, open-label, single-group study. These design features determine what kinds of statistical conclusions are available. Because there is no control group, the main information is descriptive: what was recorded among participants in the treatment group. A comparison with an untreated or alternatively treated group cannot be estimated from this design. Open-label status means masking was absent; the record does not report whether any other procedures were used to limit assessment bias.

What does a count endpoint represent?

The primary outcome is a number of severe adverse events, with events as its unit. A count records how often an event occurs during the stated observation period. It is distinct from the number of participants who experience at least one event. If a participant has multiple events, those may contribute multiple times to an event count while that participant remains a single affected participant in a participant-level summary. The registry gives participant-level adverse-event figures, but not the numerical primary event count. The methods used to define, classify, and count severe events are not reported in the registry record.

Counts can be analyzed in different ways depending on the study question and the distribution of events. General statistical explanation: a simple count model may be inadequate when the variability in counts is greater than the model expects; this is called over-dispersion. In such circumstances, an analysis that accounts for the extra variability may give more realistic uncertainty. The appropriate model also depends on whether the target is the total number of events, the chance that a participant experiences any event, or an event rate over time. The registry does not report a model or a statistical method for the primary endpoint, so no particular approach can be attributed to this study.

Why do events and participants need separate summaries?

Participant-level summaries answer how many people experienced an event, while event-level summaries answer how many events occurred. These questions can yield different results. A participant can contribute more than one event, and the number of events alone does not show how events are distributed among participants. Conversely, the count of affected participants does not describe repeated events. The registry reports 1 of 6 participants with a serious adverse event, but does not provide the primary endpoint’s event count. The two measures should not be treated as substitutes.

What can a single-group design estimate?

In general, a single-group study can describe outcomes observed in its participants. It cannot, without additional assumptions or external information, directly estimate the difference between treatment and a concurrent comparator. Changes from baseline may be of interest, but they can reflect more than treatment exposure. The registry lists secondary outcomes as changes from baseline in blood measures, organ volumes, and biomarkers, but does not report their numerical results or the analysis methods used. No causal comparison should be inferred from the design description alone.

How should uncertainty be understood?

A confidence interval is a statistical range intended to express uncertainty around an estimate under the assumptions of the method used. A narrow interval generally indicates more precision than a wide interval, while an interval’s interpretation depends on the analysis and data. The registry information does not provide a confidence interval for the primary endpoint. With a small study group, descriptive estimates may be sensitive to individual observations, and any estimate intended to generalize beyond the enrolled participants would require particular caution. The record does not report an inferential method or the assumptions used to quantify uncertainty.

What do the planning assumptions mean?

General statistical explanation: a sample-size calculation is a planning exercise that relates a proposed study size to assumptions about an effect, variability, significance level, and allocation. Such an illustration is not the same as an observed result, and it is not “observed power.” The registry’s planning assumptions describe a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation for an effect expressed as a fraction of an observed effect. Those are assumptions for a planning illustration, not a description of this single-group trial’s design. Numerical planning estimates are not reported in the registry record. They should not be mistaken for the number enrolled or for evidence about the study’s findings.

The registry records 0 analyses. It does not report a statistical analysis plan, a model for the primary endpoint, an approach to missing data, or an analysis population. Accordingly, statistical methods that might commonly be used in a trial should be understood only as general concepts, not as methods documented for this study. The posted information supports a design-level reading and limited descriptive safety interpretation, rather than a reconstruction of an unreported analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary safety endpoint and secondary outcomes involving hemoglobin, platelet count, liver and spleen volume, plasma chitotriosidase, and CCL18. When a study examines multiple outcomes, the chance of finding an apparently notable result across the set can be different from the chance for one prespecified outcome alone. General statistical explanation: multiplicity procedures can control that risk, but their choice depends on the aims and analysis plan. A multiplicity strategy is not reported in the registry record.

The registry does not provide numerical results for the listed secondary outcomes or describe whether any were formally tested. It records 0 analyses. No conclusions about secondary-outcome changes, statistical significance, or adjustment across outcomes can therefore be drawn from the information recorded. The primary outcome’s numerical result and inferential analysis are also not reported.

Missing-data handling is not reported in the registry record. The record does not say whether all enrolled participants contributed data at each assessment, how missing measurements were handled, or whether any participants discontinued or were excluded from an analysis. The enrollment figure alone does not answer those questions. Analysis populations, including whether the primary endpoint was evaluated in all enrolled participants or a defined subset, are also not reported in the registry record.

These omissions matter because the number and pattern of available observations can affect an estimate and its uncertainty. Without an account of missingness and analysis populations, the completeness of the outcome data cannot be assessed. The registry also does not report a prespecified statistical plan against which the posted results could be checked.

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: retinal detachment (16.7%).

The registry’s safety summary lists the VPRIV® (15-60 U/kg) group, with 6 participants at risk for serious adverse events and 1 affected. For other adverse events, it records 6 at risk and 6 affected. These are participant-level figures in the adverse-event summary. They do not state the total number of events, and they are not necessarily the same measure as the primary endpoint, which is titled “Number of Severe Adverse Events (SAE)” and uses events as its unit.

The summary also lists RETINAL DETACHMENT at 16.7%. The registry information recorded does not specify the denominator or provide further context for this term. The percentage should therefore be read as a listed adverse-event summary, not as a comparative risk estimate or a measure of treatment causation.

Because the study has one group and no control arm, these figures describe events recorded among participants in that group. They do not show how the same outcomes compare with another treatment or with no treatment. The primary endpoint’s numerical event count, event definitions, and analysis are not reported in the registry record. The figures are useful as descriptive safety information, but cannot by themselves establish whether an event was caused by treatment or quantify comparative safety.

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

The record establishes that a Phase 3, open-label, single-group study evaluated velaglucerase alfa in Japanese patients with Gaucher disease, with a safety-focused primary objective. It specifies a primary endpoint of severe adverse events over Baseline to week 51 and provides a limited participant-level adverse-event summary. Those details describe what the study set out to examine and some of the safety information recorded.

The available record does not report the primary endpoint’s numerical result, a confidence interval, or an inferential analysis. It also does not give numerical results for the secondary outcomes. Thus, the posted information does not allow a reader to quantify the primary endpoint, assess its precision, or evaluate changes in the listed blood, organ-volume, and biomarker outcomes.

The study’s single-group design also sets an important boundary on interpretation. Observations in the treatment group do not provide a concurrent comparison. A before-and-after change, even if numerical results were available, would not by itself demonstrate that treatment caused the change. The adverse-event summaries likewise cannot establish that the intervention caused a particular event or compare its safety with another option.

The group size and the registry’s limited outcome reporting also restrict how broadly the observations can be interpreted. The record does not report a statistical analysis plan, missing-data handling, analysis populations, or details needed to assess the completeness and precision of endpoint estimates. These gaps do not negate the descriptive information that is recorded, but they limit the conclusions that can be drawn from it.

Accordingly, the result should be understood as a registry record of study design and selected safety counts, not as a complete quantitative evaluation of the stated primary endpoint. It does not establish treatment benefit, lack of benefit, or comparative safety. Those claims would require evidence not reported in this registry record.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a stated research question and a fully reported result. The registry identifies a primary safety endpoint, its unit, and its observation timeframe, but does not report the endpoint’s numerical result or an analysis. Knowing the endpoint definition is necessary to interpret a result, yet it does not replace the result itself.

The record also illustrates why design matters. A single-group study can describe what happened among participants who received the intervention, but it lacks a concurrent comparison for estimating differences between treatment conditions. That limitation is especially relevant when interpreting safety events, which may arise for reasons other than treatment. The study’s open-label status is another design feature to keep in mind when considering how events were assessed; further safeguards are not reported in the registry record.

The distinction between event counts and participant counts is also important. The primary endpoint is expressed as a number of events, whereas the safety summary reports participants affected. Those measures answer different questions and should not be conflated. The record’s summary is descriptive, while the missing primary event count prevents a direct numerical reading of the named primary outcome.

Finally, the registry lists several secondary outcomes but does not report their numerical results or a multiplicity strategy. This underscores the need to know which outcomes were analyzed, how missing data were handled, and what analysis populations were used before interpreting a collection of trial outcomes. Those details are not reported in the registry record. The study therefore offers a useful case for reading registry information carefully: design, endpoint, analysis, and result are connected, but one cannot stand in for another.

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 principal limitation for interpreting this trial from the registry record is that the numerical result for the primary endpoint is not reported. The endpoint is defined as the number of severe adverse events from Baseline to week 51, but the record does not provide that event count, a measure of uncertainty, or a statistical analysis. The participant-level safety summary does not fill this gap because affected participants and total events are different quantities.

The study is single-group, open-label, and has no randomized comparison. This prevents a direct comparison with another treatment or a control condition and limits causal interpretation of observed events or changes. The registry does not report whether any additional procedures were used to standardize event assessment. The enrollment is recorded as 6, so the descriptive safety figures come from a small group and should not be treated as precise estimates for a broader population.

Details that would aid interpretation are not reported in the registry record: the operational definition of severe events, event adjudication procedures, participant characteristics, disease subtype, treatment adherence, discontinuations, missing-data methods, analysis populations, and the statistical analysis plan. The numerical results for the listed secondary outcomes are also not reported. The adverse-event summary lists RETINAL DETACHMENT at 16.7%, but does not give the context needed to interpret its denominator from the recorded information.

These limitations concern what can be concluded from the registry information; they do not establish that the study lacked procedures or analyses outside the information recorded. They do mean that readers cannot reconstruct the primary analysis or assess the precision and completeness of the reported safety findings from this record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study of Velaglucerase Alfa Enzyme Replacement Therapy in Japanese Patients With Gaucher Disease — NCT01614574.
• Registry record last updated 2021-06-28; status last verified 2021-06.
• Results first posted 2014-08-04.
• 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 NCT01614574, a completed Phase 3, multicenter, open-label, single-group study of velaglucerase alfa in Japanese patients with Gaucher disease. Enrollment was 6. The recorded study start date is 2012-03-02, and the primary completion date is 2013-05-25.

The primary objective was to evaluate the safety of every-other-week dosing. The primary endpoint was the number of severe adverse events from Baseline to week 51. The safety summary records 1 of 6 participants with a serious adverse event and 6 of 6 with another adverse event; RETINAL DETACHMENT is listed at 16.7%. The primary endpoint’s numerical result and statistical analysis are not reported in the registry record. Secondary outcomes include changes in blood measures, organ volumes, and biomarkers, but their numerical results are not reported in the information recorded for this study.