Survey Study for Velaglucerase Alfa (VPRIV) in Japan: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Survey Study for Velaglucerase Alfa (VPRIV) in Japan (NCT03625882), a registered phase not stated study. The primary outcome is Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAE) Following Initiation of Treatment With Velaglucerase Alfa.

2. Clinical Question

3. Trial Design

This is a post-marketing survey study of velaglucerase alfa, rather than a randomized treatment comparison. Its official title is VPRIV Drug Use-Result Survey (Japan), and the registry lists Takeda as the sponsor. The condition is Gaucher Disease. The study description includes participants who were new to VPRIV therapy and participants switched from another therapeutic agent for Gaucher disease. The registry lists enrollment as 63.

The record gives a start date of 2014-09-02 and a primary completion date of 2024-05-14, and its status is COMPLETED. The primary outcome timeframe is baseline up to the end of the study, described as 8 years. The safety analysis set is defined as all participants who received at least one dose of recombinant velaglucerase alfa intravenous infusion. The adverse-event results separately list 60 at risk for serious events and 60 at risk for other events. The record does not explain the relationship between those figures and enrollment.

The stated objective is to collect post-marketing data to determine safety and efficacy in participants with Gaucher disease who are new to therapy or switched from another therapeutic agent. Secondary outcomes include efficacy categories for changes in hemoglobin concentration, platelet counts, liver volumes, and spleen volumes; lumbar spine and femur neck bone mineral density measures; and positive anti-velaglucerase alfa antibody test results. The record lists 11 outcome measures, but does not report a randomized allocation method or a control group. Allocation is not stated. The record explicitly cautions that the arms are not a like-for-like control comparison.

Because the design is a survey and no randomized contrast is described, the study should be read as a source of observed safety and efficacy information in the surveyed participants. The registry record does not report a protocol-level statistical analysis plan or inferential analyses.

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.

Before assignment: Participants with Gaucher disease who received Recombinant Velaglucerase Alfa were enrolled. Participants received VPRIV intravenous infusion as part of a routine medical care.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set, The safety analysis set was defined as all participants who received at least one dose of Recombinant Velaglucerase Alfa intravenous infusion.

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, The safety analysis set was defined as all participants who completed the survey.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events (AEs) and Serious Adverse Events (SAE) Following Initiation of Treatment With Velaglucerase Alfa, measured over Baseline up to end of the study (8 years).

The primary endpoint counts participants with adverse events and serious adverse events following initiation of velaglucerase alfa. Its timeframe is baseline up to the end of the study, described as 8 years, and the unit is participants. An adverse event is defined in the record as an unfavorable and unintended sign, symptom, or disease temporally associated with use of a medicinal product, whether or not considered related to that product. An abnormal laboratory finding is included as an example.

A serious adverse event is an event resulting in death, being life-threatening, requiring inpatient hospitalization or prolonging an existing hospitalization, causing persistent or significant disability or incapacity, involving a congenital anomaly or birth defect, or being medically important. These definitions classify events by occurrence and seriousness; they do not establish that treatment caused an event. The record’s definition expressly includes events whether or not they are considered related to the medicinal product.

In general, participant counts are used to describe how many people experienced an event under the outcome definition. Such counts are useful for safety surveillance, where the occurrence and seriousness of reported events are central. Counts alone do not describe how quickly events occurred, the duration of exposure, or a rate adjusted for time under observation. The registry record does not report a rate-based primary endpoint or a causal comparison with a control group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record defines the primary outcome as a count of participants with adverse events and serious adverse events. It reports event categories and numbers of participants, rather than a continuous measurement such as a laboratory value. The safety analysis set is defined as participants who received at least one dose of recombinant velaglucerase alfa intravenous infusion. The adverse-event summary lists 60 at risk in each of its serious and other-event categories, alongside the reported affected counts.

What does a participant count describe?

In general, a participant count records how many people meet a stated event definition during the observation period. For a safety endpoint, the definition determines which experiences are included and how seriousness is classified. Counts can be straightforward to read, but they do not show event timing, the number of repeated events per participant, or the amount of time each participant was observed. This endpoint is specifically described as a count of participants; the registry record does not say that it counts all event episodes.

The adverse-event definition includes events temporally associated with use of a medicinal product whether or not the event is considered related to it. That wording is important: temporal association is not the same as a causal conclusion. The serious adverse-event category uses consequences such as death, life-threatening events, hospitalization, disability, congenital anomaly or birth defect, and medically important events. A seriousness classification describes the event under the record’s definition; it does not, on its own, identify why the event occurred.

Why do denominators and follow-up matter?

In general, a count is easiest to interpret when its population and observation period are clear. A count from a larger population may be higher even if the underlying chance of an event is similar. A count also does not adjust for how long participants were observed or exposed. Rates use a time-at-risk denominator, while a participant proportion uses a participant denominator; they answer different descriptive questions. The primary outcome is specified as a participant count, and the registry record does not give a rate-based estimate or participant-specific follow-up information.

The record lists enrollment as 63, while the adverse-event summary lists 60 at risk for each of its event categories. The safety set is defined by receipt of at least one dose. The registry record does not explain the relationship between enrollment, the safety analysis set, and the at-risk figures, nor does it report reasons for any difference. No denominator should be inferred beyond the figures explicitly associated with each category.

What would an interval estimate add?

In general, a confidence interval expresses the statistical uncertainty around an estimate under a specified method. It is not a guarantee that the true value lies within the interval, and its interpretation depends on the design and assumptions used. The registry record does not report confidence intervals for the posted adverse-event counts. Therefore, the precision of those counts cannot be summarized with an interval from the information in the record. No interval or other inferential result should be inferred from the counts alone.

In general, a model for event counts may need to account for variation beyond what a simple probability model expects, sometimes described as over-dispersion. That issue is relevant when modeling event counts across people or repeated events, but the registry record does not report a count model, a repeated-event analysis, or an over-dispersion assessment. The primary endpoint is a count of participants with an event, and no statistical model for it is described. These general modeling considerations should not be mistaken for methods used in this survey.

What analysis was reported?

The registry record lists no analyses. It does not report a hypothesis test, adjusted analysis, confidence interval, or statistical model for the primary outcome. The record also does not describe an analysis plan, covariate selection, subgroup method, or handling of repeated events. These details are not reported in the registry record; their absence does not establish what may or may not have been done outside the registry entry.

The record includes a planning note for sample-size illustrations. It specifies 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. It describes these as planning illustrations computed from the observed effect, not as the survey’s own design. The note states that time-to-event calculations give the total number of events using Schoenfeld, while other calculations give participants per arm. Such planning values, where reported, are not observed power and do not turn this survey into a randomized comparison. No sample-size illustration values or observed-effect estimate are reported in the registry record summarized for this study.

10. Multiplicity, Missing Data and Analysis Populations

The registry record names a primary safety outcome and multiple secondary outcomes, including efficacy categories for hemoglobin concentration, platelet counts, liver volumes, and spleen volumes; bone mineral density measures; and anti-velaglucerase alfa antibody test results. It lists 11 outcome measures. The record does not report a multiplicity strategy, such as a prespecified hierarchy, adjustment across outcomes, or another approach to interpreting multiple statistical tests. It also lists no analyses, so no multiplicity-adjusted or unadjusted inferential findings are available in the registry record.

Missing-data handling is not reported in the registry record. The entry does not describe how unavailable outcome values, incomplete follow-up, withdrawals, or missing event information were handled. It does not state whether analyses used all available observations, a defined imputation method, or another approach. As a result, the potential impact of missing observations cannot be assessed from the registry entry.

The safety analysis set is defined as participants who received at least one dose of recombinant velaglucerase alfa intravenous infusion. The registry lists enrollment as 63 and lists 60 at risk in each adverse-event category. It does not explain the relationship among these figures or provide a participant flow accounting. The named safety set provides a population definition, but the record does not give separate analysis-population definitions for the secondary outcomes. It also does not state whether all participants in the safety set contributed data to every outcome measure.

These omissions limit assessment of how outcome selection, incomplete data, and analysis-population choices may affect interpretation. The absence of information in the registry record should not be taken as evidence that a particular method was or was not used elsewhere.

11. 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 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 (5.0%), respiratory failure (5.0%), sepsis (3.3%), urinary tract infection (3.3%), myoclonic epilepsy (3.3%).

The adverse-event summary reports 27 participants affected by serious adverse events and 31 affected by other adverse events, with 60 at risk in each category. It also lists 14 deaths. These figures should be read as separate reported entries. The registry record does not say whether the same participants appear in more than one category, or how deaths overlap with serious adverse events. They should not be added to create a total number of affected participants.

The most frequently listed serious-event terms include pneumonia and respiratory failure, each reported as 5.0%. Sepsis, urinary tract infection, myoclonic epilepsy, and vesicoureteric reflux are each reported as 3.3%. The adverse-event summary does not identify the denominator for these percentages, so they should be read as the term percentages recorded rather than converted to counts or compared against another population.

The event definitions include events whether or not considered related to the medicinal product. Thus, the counts and terms describe reported safety events under the registry definitions; they do not establish treatment causation. The record does not provide event timing, individual follow-up duration, or a comparison group for interpreting these figures as relative risks.

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

The registry record provides a descriptive account of safety events reported in a Japanese post-marketing survey of velaglucerase alfa. It lists counts for participants affected by serious and other adverse events, a death count, and selected serious-event terms with percentages. The primary endpoint is a participant count over a timeframe described as baseline to the end of the study, or 8 years. These registry entries characterize what the registry reports for the survey; they are not a randomized estimate of the difference between treatments.

The record’s adverse-event definition includes events that are temporally associated with use of the medicinal product, whether or not considered related. Consequently, a recorded event count should not be interpreted as a count of events caused by velaglucerase alfa. Nor does a count by itself describe an event rate, severity beyond the stated seriousness classification, or the timing and duration of an event. The listed serious-event terms and percentages also lack a denominator in the adverse-event summary, limiting further interpretation.

The survey included participants who were new to VPRIV therapy or had switched from another therapeutic agent, but the registry does not report a randomized control group or a like-for-like comparison. Any difference between treatment histories or participant groups cannot be interpreted as a treatment effect from these registry entries. The registry lists no analyses, confidence intervals, or adjusted estimates. Statistical precision and the role of other factors therefore cannot be assessed from the posted results.

The outcome counts are relevant as post-marketing safety descriptions, but they do not answer whether velaglucerase alfa caused an event, whether its event frequency differs from another therapy, or how an individual participant’s risk compares with that of another person. The registry record also does not report missing-data methods or participant-level follow-up. These limits define what can and cannot be concluded from the posted information, without altering the reported counts.

13. Why This Trial Matters Statistically

Post-marketing surveys address questions about treatment use and safety in clinical practice after a medicinal product is in use. This registry record is statistically informative because it makes the outcome definition, safety population definition, and observed adverse-event counts explicit. It also distinguishes adverse events from serious adverse events and defines seriousness using clinical consequences such as hospitalization, life-threatening events, and death. Those definitions help readers understand what the reported categories represent.

The study also illustrates a central issue in interpreting observational safety data: event counts are descriptive unless the design and analysis support a comparison. The record does not describe random allocation or a like-for-like control group, and it cautions against treating the arms as a control comparison. The figures can therefore be read as counts recorded in the survey, but not as a randomized estimate of relative treatment effects. This distinction matters whenever registry results are used to characterize safety.

Another important statistical point is that a count needs context. The record specifies a broad observation timeframe and defines a safety analysis set, while its adverse-event summary separately lists the number at risk. It does not report individual time under observation, reasons for the difference between enrollment and the at-risk figures, or missing-data handling. Such details affect how fully counts can be interpreted, and they are not recoverable from the reported figures alone.

Finally, the registry lists secondary outcomes across blood measures, organ volumes, bone mineral density, and antibody testing, but does not report analyses or a multiplicity strategy. A broad outcome set can answer several descriptive questions, while also making a prespecified analysis plan important for interpreting multiple findings. Because that plan is not reported in the registry record, the results should be read within the limits of the posted definitions and counts.

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 design limitation for comparative interpretation is that this is a post-marketing survey, not a stated randomized comparison. Allocation is not stated, and the registry cautions that the arms are not a like-for-like control comparison. The participant group includes people new to VPRIV therapy and people switched from another Gaucher disease therapeutic agent, but the record does not provide a comparative analysis between those histories.

The enrollment figure is 63, whereas the serious and other adverse-event summaries each list 60 at risk. The safety analysis set is defined by receipt of at least one dose, but the registry does not explain the relationship among these numbers or provide a participant flow account. Reasons for any difference are not reported in the registry record. The entry also does not describe participant-level follow-up, event timing, or the amount of time each person was observed.

The registry record does not report a statistical analysis plan, inferential analyses, confidence intervals, missing-data methods, or a multiplicity strategy. It does not state how missing observations or incomplete outcome collection were handled. The adverse-event summary gives percentages for selected serious-event terms but does not identify their denominator. The posted information therefore does not support recalculating term counts or assessing the uncertainty around those percentages.

The record lists 11 outcome measures, but the available descriptions do not provide detailed results for the named secondary outcomes. The primary outcome is a participant count, not a time-adjusted rate or a causal contrast. These limitations are specific to the information recorded for this survey and restrict what can be inferred beyond the descriptive safety information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Survey Study for Velaglucerase Alfa (VPRIV) in Japan — NCT03625882.
• Registry record last updated 2026-03-04; status last verified 2026-02.
• Results first posted 2025-01-10.
• 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

NCT03625882 is the registry record for the VPRIV Drug Use-Result Survey (Japan), sponsored by Takeda. The study concerns Gaucher Disease and describes a post-marketing survey of participants who were new to VPRIV therapy or switched from another therapeutic agent. The record lists enrollment as 63, a start date of 2014-09-02, a primary completion date of 2024-05-14, and status COMPLETED.

The primary outcome counts participants with adverse events and serious adverse events from baseline through the end of the study, described as 8 years. The safety analysis set includes participants who received at least one dose of recombinant velaglucerase alfa intravenous infusion. The adverse-event summary lists 27 affected by serious events, 31 affected by other events, and 14 deaths; the record also lists selected serious-event terms with percentages.

The registry describes efficacy and antibody outcomes as secondary measures. It does not report randomized allocation, a like-for-like control comparison, analyses, missing-data methods, or a statistical analysis plan. The posted event information is therefore descriptive and should be interpreted within those limits.