This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study (NCT02525861), a randomized phase 3 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Potentially Related to Presence of Particle Load in the GLASSIA Solution.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02525861 |
| Phase | Phase 3 |
| Condition | Alpha1-antitrypsin Deficiency |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 34 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Baxalta now part of Shire |
| Results posted | Yes |
2. Clinical Question
Population
Participants with alpha1-antitrypsin deficiency and emphysema due to congenital deficiency were studied. The registry record reports an enrollment of 34. The primary endpoint’s safety analysis set included enrolled participants who received any amount of investigational product, regardless of protocol deviations or non-adherence to study procedures.
Intervention
Participants received GLASSIA, an alpha1-proteinase inhibitor augmentation therapy, by weekly intravenous infusion. The planned regimen was 60 mg/kg body weight of active alpha1-proteinase inhibitor protein for 25 weeks. The product was administered by in-line filtration, and the study also assessed alpha1-proteinase inhibitor levels and biomarkers in epithelial lining fluid.
Comparator
The comparison was between a GLASSIA lot with particle loads at the high end and a lot with particle loads at the low end within the normal range. Both cohorts received GLASSIA; the registry record does not describe a placebo or untreated comparison group.
Primary question
From the start of study treatment through Week 26, how many participants experienced a treatment-emergent adverse event considered potentially related to particle load in the GLASSIA solution? For this endpoint, the qualifying events were embolic or thrombotic events. The posted results report no such participants in either cohort.
3. Trial Design
This was a Phase 3 randomized, quadruple-masked, parallel-group study. The registry record describes two cohorts, each receiving weekly intravenous GLASSIA, with the product lots differing in particle-load range. Cohort I received a lot representing the high end of particle loads; Cohort II received a lot representing the low end within the normal range. The described treatment regimen was 60 mg/kg body weight of active alpha1-proteinase inhibitor protein, administered at 0.2 ml/kg/min for 25 weeks. Cohort I’s arm description is truncated in the registry record, so its infusion details beyond the text recorded there are not reported in the registry record.
Randomization and masking are recorded, but the method used to generate the allocation sequence, conceal allocation, or maintain masking is not reported in the registry record. The record does not state which participant groups or study personnel were included in the quadruple masking. It also does not report a separate control treatment: the comparison is between the two GLASSIA lot particle-load ranges.
The trial enrolled 34 participants. The posted primary endpoint results give arm sizes of 18.0 in the high-end cohort and 16.0 in the low-end cohort. The study is marked completed. Its recorded start date is 2016-03-08 and its primary completion date is 2020-07-29.
The stated study purpose included safety and potential immunogenicity, as well as assessment of alpha1-proteinase inhibitor levels and biomarkers in epithelial lining fluid after treatment. The registry record lists secondary outcomes concerning treatment-emergent adverse events, clinically significant laboratory-value shifts, and treatment-emergent seroconversion or positive nucleic acid testing for Parvovirus B19. Further details about the rationale for the selected enrollment or the allocation between cohorts 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.
Before assignment: A total of 34 participants were randomized and received the study treatment.
Overall Study
| Stage | Cohort I: GLASSIA (High-end) | Cohort II: GLASSIA (Low-end) |
|---|---|---|
| STARTED | 18 | 16 |
| COMPLETED | 17 | 14 |
| NOT COMPLETED | 1 | 2 |
Reasons for not completing this period:
| Reason | Cohort I: GLASSIA (High-end) | Cohort II: GLASSIA (Low-end) |
|---|---|---|
| Adverse Event | 1 | 0 |
| Withdrawal by Subject | 0 | 1 |
| Physician Decision | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Safety analysis set consisted of all enrolled participants who received any amount of IP, regardless of protocol deviations or non-adherence to study procedures.
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 consisted of all enrolled participants who received any amount of investigational product (IP), regardless of protocol deviations or non-adherence to study procedures.
| Characteristic | Unit | Cohort I: GLASSIA (High-end) | Cohort II: GLASSIA (Low-end) | Total |
|---|---|---|---|---|
| Participants analysed | 18 | 16 | 34 | |
| Age, Continuous | Years | 57.9 (SD 8.95) | 58.9 (SD 9.32) | 58.4 (SD 9.00) |
| Sex: Female, Male: Female | Participants | 8 | 6 | 14 |
| Sex: Female, Male: Male | Participants | 10 | 10 | 20 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 2 | 3 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 17 | 14 | 31 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): White | Participants | 18 | 16 | 34 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Potentially Related to Presence of Particle Load in the GLASSIA Solution, measured over From start of study treatment up to Week 26.
| Element | Registry entry |
|---|---|
| Result type | Count Of Participants |
| Measure of spread | not applicable |
| Unit | Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint counts participants with treatment-emergent adverse events considered potentially related to particle load in the GLASSIA solution. The registry definition treats an adverse event as an untoward medical occurrence after investigational product administration, whether or not it has a causal relationship with treatment. An event occurring on or after the first infusion is considered treatment-emergent. For the particle-load-related endpoint, the qualifying events are embolic or thrombotic events.
This endpoint focuses on a specific safety concern rather than counting all adverse events. In general, a defined event count can make a safety comparison more interpretable by specifying which events are relevant to the question. It does not, by itself, establish that an event was caused by treatment; the registry definition uses the phrase “potentially related,” and adverse events need not be causally related to treatment.
The timeframe runs from the start of study treatment up to Week 26. The reported result is a participant count, not a measure of event severity, duration, or recurrence. A participant-level count also does not convey how many total events occurred if an individual could experience more than one event. Event-level counts and details for this endpoint are not reported in the registry record.
The posted endpoint value is 0.0 in each cohort. This means no participants were reported with a qualifying event in either group during the stated timeframe. It should be read as an observed count in this study, not as evidence that such events cannot occur.
7. Results Posted in the Registry
- Cohort II: GLASSIA (Low-end): 0.0% (0/16) versus 0.0% (0/18) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
Risk difference: Cohort II: GLASSIA (Low-end)
95% CI: 0.0 to 0.0 percentage points
Recalculated from the posted summary statistics
8. Statistical Interpretation
The primary endpoint results are 0.0 participants in the high-end particle-load cohort and 0.0 in the low-end cohort. The registry’s unadjusted risk-difference comparison is 0.0, with a reported confidence interval from 0.0 to 0.0. The observed data therefore show no difference in the number of participants meeting this particular endpoint. Because there were no qualifying events in either group, the result does not reveal whether the particle-load ranges have different risks in a broader population.
The comparison is specific to two groups treated with GLASSIA. It does not compare GLASSIA with placebo or no treatment, and it cannot estimate a treatment effect relative to those alternatives. Nor does this endpoint summarize all safety outcomes: the registry separately lists outcomes for treatment-emergent adverse events, laboratory-value shifts, and Parvovirus B19 findings.
The reported endpoint concerns embolic or thrombotic events considered potentially related to particle load. Other adverse events can occur without meeting that definition. The safety record reports serious adverse events in each cohort, as well as other adverse events, so the zero primary-endpoint count should not be read as meaning that no adverse events occurred. The broader adverse-event counts and their definitions need to be considered separately.
A confidence interval expresses statistical uncertainty around an estimated quantity under the method used to construct it. Here, the posted risk-difference interval has endpoints of 0.0 and 0.0. With zero qualifying events in both groups, that displayed interval does not establish that the underlying risks are exactly equal or that clinically important differences are ruled out. The confidence-interval method is not reported in the registry record, and the displayed interval should be interpreted in light of the limited event information.
The registry record does not report a p-value for this comparison, an adjusted analysis, or a prespecified threshold for interpreting a difference. It also does not report a sample-size justification or an inferential conclusion about equivalence. The most direct interpretation is descriptive: no qualifying primary-endpoint event was recorded in either cohort over the stated follow-up period, while the precision and generalizability of that observation remain limited.
9. Statistical Methods Explained
The primary outcome is a binary participant-level event measure: each person either met the endpoint definition during the stated follow-up or did not. The posted results give the number of participants in each cohort with a qualifying event. The high-end cohort has a reported event count of 0.0 among 18.0 participants, and the low-end cohort has 0.0 among 16.0 participants. The registry comparison expresses the contrast as a risk difference, which is the difference between the two groups’ event proportions. Its posted estimate is 0.0.
What does a risk difference describe?
In general, a risk difference compares the proportion of participants experiencing an event in one group with the proportion in another. A value of zero indicates that the two observed proportions are the same. It is an absolute measure, rather than a relative comparison. When there are no events in either group, the observed proportions are both zero and the absolute difference is also zero. This describes the observed data; it does not prove that the underlying event probabilities are identical.
How should the confidence interval be read?
The posted confidence interval for the risk difference runs from 0.0 to 0.0. In general, a confidence interval describes the range of values compatible with the data under a specified statistical procedure and its assumptions. Its width is often used to discuss precision: a narrower interval indicates less uncertainty according to that procedure. However, the construction method for this interval is not reported in the registry record. In a dataset with no events in either group, an interval displayed with both endpoints at zero should not be taken as proof that uncertainty about the true risks has disappeared.
The registry comparison reports no p-value. A p-value, in general, measures how incompatible observed data are with a specified null hypothesis under a statistical model; it is not a direct measure of clinical importance or the probability that a treatment effect is real. Without a reported p-value or analysis method, there is no basis to describe this result as statistically significant or not statistically significant. The descriptive event counts and stated interval are the appropriate posted quantities to interpret.
What can randomization contribute?
In general, random allocation can help make groups comparable with respect to measured and unmeasured characteristics, on average. It does not guarantee that groups will be balanced in a small study, and it cannot compensate for missing data, outcome misclassification, or limited information about rare events. The registry records randomized allocation but does not report the sequence-generation or concealment procedures, so those aspects cannot be assessed from the record.
Both groups received GLASSIA. The randomized contrast therefore concerns the high-end versus low-end particle-load range of the product lots, not GLASSIA versus an untreated group. Interpretation should stay within that comparison and the endpoint definition. The study’s masking is recorded as quadruple, but which roles were masked and how masking was implemented are not reported in the registry record.
What do planning illustrations mean?
Any sample-size illustrations associated with the posted results are planning calculations, not observed power. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect defined as a fraction of the observed effect. Such calculations can illustrate planning under specified assumptions. They do not show the probability that this completed trial detected an effect, and they are not the trial’s original sample-size justification. The trial’s own sample-size justification is not reported in the registry record.
In general, planning based on an observed effect can be unstable when the observed event pattern contains no events, as it does for this primary endpoint. No numerical planning estimate or alternative effect assumption should be inferred from the posted event counts. The registry record does not report an interim-analysis plan, stopping rule, or detailed statistical analysis plan. Those elements should not be assumed when interpreting the results.
10. Confidence Intervals and Precision
The primary comparison’s posted risk-difference estimate is 0.0, and its confidence interval extends from 0.0 to 0.0. These values describe the registry’s reported comparison. They do not provide evidence that the actual event risks in the two populations are known exactly. The interval method is not reported in the registry record, and both cohorts had zero observed events for this narrowly defined endpoint.
Precision depends on how much information the data contain about the quantity being estimated. For an uncommon event, a small study may observe no events even when the underlying risk is not zero. When that happens, the observed difference can be zero while uncertainty about future or population-level event rates remains. The confidence interval as posted should therefore be considered alongside the group sizes, event definition, and absence of qualifying events, rather than interpreted as a guarantee of no difference.
The endpoint is limited to embolic or thrombotic treatment-emergent adverse events potentially related to particle load and covers the period from treatment start through Week 26. It does not capture every safety outcome or outcomes beyond that timeframe. The registry record does not report the number of participants with missing primary-outcome assessments, how missing observations were handled, or the method used to calculate the interval. These omissions limit assessment of the precision and robustness of the estimate.
Zero observed events is a descriptive finding, not proof of zero risk. The posted data do not establish equivalence between the cohorts or rule out differences that the study may have been unable to estimate precisely. No margin for equivalence or non-inferiority is reported in the registry record.
11. Multiplicity, Missing Data and Analysis Populations
The registry record lists secondary outcomes concerning treatment-emergent adverse events, shifts from normal or clinically non-significant baseline laboratory values to clinically significant values, and treatment-emergent seroconversion or positive nucleic acid testing for Parvovirus B19. It also records multiple outcome measures. Testing or estimating several outcomes can raise multiplicity concerns: in general, the more statistical comparisons made, the greater the chance of at least one apparently notable result arising by chance if each is assessed separately.
Whether multiplicity was controlled, and by what method, is not reported in the registry record. The record also does not report a hierarchy for testing outcomes or identify which secondary analyses were considered confirmatory. The primary endpoint should therefore be distinguished from the other safety outcomes, and unreported adjustment procedures should not be assumed.
The primary endpoint population is described as the safety analysis set: enrolled participants who received any amount of investigational product, regardless of protocol deviations or non-adherence to study procedures. The registry record does not provide a detailed account of exclusions, endpoint ascertainment for each participant, or departures from the planned treatment schedule. It does not state whether all randomized participants were included in the primary analysis.
Missing-data counts and handling are not reported in the registry record. It is therefore not possible to assess whether any participants lacked endpoint information, whether missingness differed between cohorts, or how missing values might affect the result. No imputation method, sensitivity analysis, or missing-data assumption is reported. These details matter because a zero event count is most informative when outcome status is known for the participants in the analysis population.
The registry record also does not report an interim-analysis plan, early-stopping boundaries, or the detailed statistical analysis plan. These absences do not alter the posted counts, but they limit evaluation of how outcome definitions, missing information, and multiple analyses were handled.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| GLASSIA (High-end) | 1 | 18 | 5.6% |
| GLASSIA (Low-end) | 1 | 16 | 6.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| GLASSIA (High-end) | 0 of 18 |
| GLASSIA (Low-end) | 0 of 16 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| GLASSIA (High-end) | 13 of 18 |
| GLASSIA (Low-end) | 9 of 16 |
Most frequent serious adverse event terms
| Event term | Organ system | GLASSIA (High-end) | GLASSIA (Low-end) |
|---|---|---|---|
| Influenza | Infections and infestations | 1 of 18 | 0 of 16 |
| Pneumonia | Infections and infestations | 1 of 18 | 0 of 16 |
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | 0 of 18 | 1 of 16 |
Most frequent non-serious adverse event terms
| Event term | Organ system | GLASSIA (High-end) | GLASSIA (Low-end) |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 5 of 18 | 1 of 16 |
| Diarrhoea | Gastrointestinal disorders | 3 of 18 | 0 of 16 |
| Upper respiratory tract infection | Infections and infestations | 0 of 18 | 3 of 16 |
| Back pain | Musculoskeletal and connective tissue disorders | 2 of 18 | 1 of 16 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 2 of 18 | 1 of 16 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 2 of 18 | 1 of 16 |
| Nausea | Gastrointestinal disorders | 2 of 18 | 0 of 16 |
| Vomiting | Gastrointestinal disorders | 2 of 18 | 0 of 16 |
| Bronchitis | Infections and infestations | 1 of 18 | 1 of 16 |
| Sinusitis | Infections and infestations | 0 of 18 | 2 of 16 |
Serious events with the highest arm-level rate: pneumothorax (6.2%), influenza (5.6%), pneumonia (5.6%).
The serious adverse-event figures are participant counts in the adverse-event record. The high-end cohort reports 1 serious adverse event among 18 participants at risk, and the low-end cohort reports 1 among 16 participants at risk. The record reports zero deaths in each cohort. It also lists other adverse events for 13 participants in the high-end cohort and 9 in the low-end cohort.
These safety counts are separate from the primary endpoint. The primary endpoint is restricted to treatment-emergent embolic or thrombotic events considered potentially related to particle load; the serious adverse-event counts are broader. Thus, serious adverse events can be reported even when the primary endpoint count is zero. The counts alone do not establish whether an event was caused by GLASSIA, nor do they describe event duration, severity beyond the serious classification, or recurrence.
The registry lists Pneumothorax at 6.2%, Influenza at 5.6%, and Pneumonia at 5.6% among the top serious terms. The denominator and precise context for these term percentages are not reported in the registry record. They should not be treated as directly comparable cohort-specific rates without that information. The figures provide a safety description, not a causal comparison between the two particle-load groups.
13. What the Result Does, and Does Not, Mean
The central result is straightforward: no participant in either GLASSIA cohort was reported to have a treatment-emergent embolic or thrombotic event potentially related to particle load during the period from treatment start through Week 26. The posted risk difference is 0.0, with a confidence interval from 0.0 to 0.0. This is a description of the observed primary endpoint in the study population.
The result does not show that GLASSIA has no safety risks. The endpoint captures only a defined category of events, and the registry reports serious and other adverse events separately. It also does not show that the two particle-load ranges have identical underlying risks. No events in either cohort leave little direct information for estimating differences in this specific outcome beyond the reported point estimate.
The comparison does not estimate GLASSIA’s effects relative to placebo, no treatment, or another therapy. Each cohort received GLASSIA, and the planned contrast was between product lots representing different particle-load ranges. The result should not be generalized beyond that comparison without additional evidence.
The study also aimed to assess immunogenicity and alpha1-proteinase inhibitor levels and biomarkers in epithelial lining fluid. The primary endpoint result does not answer those other questions. Although the registry lists secondary safety outcomes, the primary result alone cannot be used to characterize every outcome collected in the trial.
More broadly, a completed randomized study can provide useful structured observations while still leaving uncertainty about uncommon outcomes. Interpretation depends on the endpoint definition, follow-up period, analysis population, missing-data handling, and the precision of the estimate. Several of those analytic details are not reported in the registry record. The appropriate conclusion is therefore limited: the posted primary outcome contains no qualifying events in either cohort, while it does not establish zero risk, equivalence, or a comparison against an untreated group.
14. Why This Trial Matters Statistically
This trial is statistically informative because it makes a defined comparison within a treated population: GLASSIA lots at different particle-load ranges. That is a different question from whether GLASSIA is effective or safe compared with no treatment. Keeping the contrast clear prevents the primary result from being interpreted as answering a broader treatment question.
The endpoint also illustrates a common challenge in safety analysis. A focused event definition can be clinically relevant, but rare or narrowly defined events may not occur during a study even when the study observes other adverse events. Here, the primary particle-load-related count is zero in both cohorts, while the broader safety record includes serious and other adverse events. Those findings are not contradictory; they concern different outcome definitions.
The comparison further shows why point estimates and precision must be read together. The risk difference is 0.0, and the posted confidence interval also has endpoints of 0.0. Yet the absence of observed events does not establish equality of underlying risks. Event-free data can limit what can be learned about differences, particularly for a specific safety outcome.
Finally, the record demonstrates the value of clear reporting about analysis populations, missing outcomes, statistical methods, and multiplicity. The safety population is defined, but important details about missing-data handling, interval construction, and multiplicity procedures are not reported in the registry record. Those details affect how readers assess the strength and limits of an estimate. The result is most useful when treated as a precise description of the posted observations, rather than as a universal claim about risk.
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 primary endpoint is specific to treatment-emergent embolic or thrombotic events considered potentially related to particle load. It does not represent all adverse events, and its timeframe ends at Week 26. The result therefore does not address other safety outcomes or events outside the recorded follow-up period.
There were no reported qualifying events in either cohort. This leaves the primary comparison with limited event information, even though a risk difference and confidence interval are posted. The interval method is not reported in the registry record, and its displayed endpoints should not be understood as proof that the groups’ underlying risks are identical.
The study compares two GLASSIA particle-load ranges, not GLASSIA with placebo or no treatment. The result cannot answer a treatment-versus-no-treatment question. The group sizes reported for the primary analysis are 18.0 and 16.0, and the registry record does not report a sample-size justification for the trial or an equivalence margin.
Important analytic details are not reported in the registry record, including the method for random-sequence generation, allocation concealment, the specific roles included in quadruple masking, missing-data handling, the confidence-interval method, multiplicity adjustment, and a detailed statistical analysis plan. The registry also does not report whether interim analyses or stopping rules were used. These gaps limit independent evaluation of the analysis and of possible bias.
The primary safety population includes enrolled participants who received any amount of investigational product, regardless of protocol deviations or non-adherence. The record does not give a participant-level account of endpoint completeness or treatment adherence. The adverse-event term percentages are listed without their denominator context. These limitations call for a narrow reading of the posted counts rather than broader conclusions about comparative or long-term safety.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: GLASSIA Safety, Immunogenicity, and Bronchoalveolar Lavage Study — NCT02525861.
- Registry record last updated 2021-10-14; status last verified 2021-07.
- Results first posted 2021-10-14.
- 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.
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19. Record Summary
The registry record describes a completed Phase 3 randomized, quadruple-masked, parallel-group study in participants with alpha1-antitrypsin deficiency. It compared weekly intravenous GLASSIA from lots representing high-end and low-end particle-load ranges. The planned regimen was 60 mg/kg body weight of active alpha1-proteinase inhibitor protein for 25 weeks.
The primary endpoint was the number of participants with treatment-emergent embolic or thrombotic events potentially related to particle load, from treatment start through Week 26. The posted count was 0.0 in each cohort. The risk-difference estimate was 0.0, with a confidence interval from 0.0 to 0.0. The registry separately reports serious and other adverse events.
The result describes the observed primary outcome and does not establish zero risk, equivalence, or a comparison with no treatment. Details on missing-data handling, multiplicity, the interval method, and several design procedures are not reported in the registry record.