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 A Safety and Dose Ranging Study of Idursulfase (Intrathecal) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Hunter Syndrome Who Have Central Nervous System Involvement and Are Receiving Treatment With Elaprase® (NCT00920647), a randomized phase 1, phase 2 study. The primary outcome is Number of Serious Adverse Event (SAE).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00920647 |
| Phase | Phase 1, Phase 2 |
| Condition | Hunter Syndrome |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 16 |
| Arms in the primary outcome | 4 |
| Lead sponsor | Shire |
| Results posted | Yes |
2. Clinical Question
Population
Pediatric patients with Hunter syndrome and cognitive impairment are described in the official title. The study description focuses on patients with central nervous system involvement who were receiving treatment with Elaprase. The registry lists 16 enrolled participants.
Intervention
The intervention was intrathecal idursulfase, administered using an intrathecal drug delivery device. The registry lists monthly administration at doses of 1 mg, 10 mg, or 30 mg. The study description says intrathecal administration was in conjunction with intravenous Elaprase.
Comparator
The comparator was a control group described as untreated patients. The registry does not give further detail about the control group’s background treatment or whether its care differed from the intervention groups in other ways.
Primary question
The primary outcome was the number of serious adverse events during 6 months in the ITT population identified in the registry as having abnormalities any time post-baseline. The central question is descriptive: how many serious adverse events were posted for each group? The registry does not report a formal statistical comparison between groups or an estimate of the relative effect of one dose versus another.
The study was described as a Phase I/II safety and ascending-dose-ranging study. Its stated purpose included obtaining safety and exposure data, along with secondary and exploratory outcome measures, to inform the design of subsequent clinical trials. That purpose is distinct from establishing a definitive comparative effect. The posted primary outcome is an event count, and the listed group counts should be read as descriptive results rather than as evidence of a tested difference.
3. Trial Design
The registry describes a randomized, unmasked, parallel Phase I/II study. It lists 16 enrolled participants and four groups: control, intrathecal idursulfase at 1 mg, intrathecal idursulfase at 10 mg, and intrathecal idursulfase at 30 mg. The posted primary-outcome summaries list 4 participants for each group. Randomization details, including the allocation procedure and any allocation concealment, are not reported in the registry record.
The intervention groups received monthly intrathecal idursulfase through an intrathecal drug delivery device. The official title describes intrathecal idursulfase-IT as administered in conjunction with intravenous Elaprase. The control arm is described as untreated patients. Further detail about background treatment by group is not reported in the registry record, so the precise treatment contrast should not be inferred beyond those descriptions.
The registry identifies Hunter syndrome as the condition and describes a pediatric population with central nervous system involvement and cognitive impairment. The brief study description explains that the intrathecal formulation was developed for delivery into cerebrospinal fluid, while the intravenous formulation was not expected to cross the blood-brain barrier at therapeutic levels. This explains the rationale for studying a different route of administration; it does not establish a clinical effect.
The study start date is 2009-11-18, the primary completion date is 2012-10-29, and the status is completed. The registry does not report the planned duration of follow-up for every outcome beyond the primary outcome’s 6-month timeframe. The specific randomization ratio, eligibility criteria in full, dose-escalation rules, and details of how participants were assigned to the dose groups 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
| Stage | Control | Idursulfase IT (1 mg) | Idursulfase IT (10 mg) | Idursulfase IT (30 mg) |
|---|---|---|---|---|
| STARTED | 4 | 4 | 4 | 4 |
| COMPLETED | 4 | 4 | 4 | 4 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: Abnormalities Any Time Post-baseline ITT Population
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.
| Characteristic | Unit | Control | Idursulfase IT (1 mg) | Idursulfase IT (10 mg) | Idursulfase IT (30 mg) | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 4 | 4 | 4 | 4 | 16 | |
| Age, Categorical: <=18 years | Participants | 4 | 4 | 4 | 4 | 16 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous | years | 8.64 (SD 2.462) | 5.61 (SD 1.799) | 4.34 (SD 0.829) | 6.91 (SD 1.678) | 6.38 (SD 2.294) |
| Sex: Female, Male: Female | Participants | 0 | 0 | 0 | 0 | 0 |
| Sex: Female, Male: Male | Participants | 4 | 4 | 4 | 4 | 16 |
| Region of Enrollment: United States | Participants | 3 | 2 | 4 | 2 | 11 |
| Region of Enrollment: United Kingdom | Participants | 1 | 2 | 0 | 2 | 5 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Serious Adverse Event (SAE), measured over 6 months.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | events |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of serious adverse events during 6 months. The registry identifies the population as the ITT population with abnormalities any time post-baseline. An event count records how many events occurred; it is not the same measure as the number of participants who experienced at least one serious adverse event. A participant may experience more than one event, so the event count and the affected-participant count answer different questions.
Safety outcomes are used in early-phase studies to describe adverse events observed during exposure to an intervention. In general, reviewing both event counts and the number of participants affected can help distinguish repeated events in some participants from events affecting different participants. The registry posts the primary outcome as a count of serious adverse events by group, while the safety listing separately reports the number of participants with serious adverse events.
The posted event counts are 0 in the control group, 8 in the 1 mg group, 3 in the 10 mg group, and 3 in the 30 mg group. Each group has 4 participants listed for this endpoint. These summaries do not provide event-level timing, duration, severity grading beyond the serious classification, or attribution to treatment. Those details are not reported in the registry record. The record also does not report a formal between-group estimate or uncertainty interval for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary outcome is reported as serious adverse-event counts over 6 months. The registry lists 0 events in the control group, 8 in the 1 mg group, 3 in the 10 mg group, and 3 in the 30 mg group. The primary-outcome summaries list 4 participants in each group. These are descriptive counts; they do not, by themselves, establish whether the groups differ beyond what could occur by chance.
The separate safety summary reports the number of participants with at least one serious adverse event: 0 of 4 in the control group, 3 of 4 in the 1 mg group, 2 of 4 in the 10 mg group, and 2 of 4 in the 30 mg group. This is not interchangeable with the event-count outcome. For example, the 1 mg group has 8 serious adverse events but 3 participants reported with serious adverse events. The registry does not provide enough event-level detail to determine how the events were distributed among affected participants.
For other adverse events, the registry reports 4 of 4 participants affected in each group. The listed serious adverse-event terms are implant site infection at 50.0%, dehydration at 25.0%, vomiting at 25.0%, device dislocation at 25.0%, complication of device insertion at 25.0%, and device breakage at 25.0%. The record does not describe the denominator or calculation behind these term percentages, so they should be read as reported rather than reinterpreted as group-specific risks.
No p-value, confidence interval, or adjusted treatment estimate is reported for the primary outcome. The registry lists 0 analyses. It also does not report whether any observed events were judged related to study treatment, how serious events were defined or adjudicated, or whether events were recurrent. Consequently, these summaries support a description of what was recorded in each group, but not a formal claim of a difference between doses or versus control.
The group sizes are small, and the outcome is a count. General statistical considerations are that estimates from small groups are imprecise, while counts can be influenced by whether a few participants experience multiple events. Without event-level data and an inferential analysis, the numerical pattern should not be treated as a reliable ranking of doses. The registry’s stated aim was to gather safety and exposure information for planning later trials, rather than to provide a definitive comparison.
9. Statistical Methods Explained
A randomized parallel design assigns participants to one of several groups and follows those groups concurrently. Randomization can reduce systematic differences at assignment, on average, but it does not guarantee that small groups will be alike in every important characteristic. The registry identifies the design as randomized and parallel, but does not report the randomization procedure, concealment, or the intended allocation ratio. No further details about those methods should be inferred.
The study is labeled Phase I/II and described as a safety and ascending dose-ranging study. In general, early-phase studies commonly emphasize safety, tolerability, and exposure information, while dose-ranging can examine observations across selected dose levels. That general description does not establish a particular dose-escalation algorithm or statistical model. Such details are not reported in the registry record. The intervention groups are listed at 1 mg, 10 mg, and 30 mg, with monthly delivery by an intrathecal drug delivery device; a formal trend analysis across these doses is not reported.
The primary outcome is a count of serious adverse events. General statistical methods for counts may use a Poisson model when events are expected to occur independently at a stable average rate over a defined exposure period. If variability in counts exceeds the model’s assumptions, over-dispersion can make standard errors too small and uncertainty appear narrower than warranted; other models may be considered in such settings. These are general methodological points, not descriptions of the analysis used in this study. The registry does not report a model, an event-rate analysis, exposure-time adjustment, or an inferential comparison.
Counts and affected-participant summaries answer different questions. An event count includes repeated events when they occur, whereas a participant count records whether a participant experienced an event at least once. In this study, the primary outcome lists event totals, and the safety summary separately gives the number of participants with serious adverse events. Neither summary supplies the event-level record needed to examine recurrence, timing, or clustering within participants. No event-level analysis is reported in the registry record.
In general, an uncertainty interval around a treatment estimate describes a range of values compatible with the data and the specified statistical method. It communicates precision as well as the direction and magnitude of an estimated contrast. A p-value, when reported, describes the compatibility of data with a specified null model; it is not a measure of clinical importance. Neither a confidence interval nor a p-value for a between-group comparison of the primary outcome is reported in the registry. Thus, no inferential precision for such a contrast can be assessed from the posted summary.
The registry describes an ITT population for the primary endpoint. In general, an intention-to-treat approach analyzes participants according to assigned groups, regardless of adherence, when the relevant population and data are defined. The registry wording identifies the population for the outcome but does not explain the analysis-set rules, how assignment was handled, or how participants with missing outcome data were treated. Those particulars are not reported in the registry record.
The record lists 11 outcome measures and 5 posted secondary outcomes, including cerebrospinal-fluid glycosaminoglycans at Week 27, idursulfase levels in cerebrospinal fluid, serum concentrations after administration, and percentage change in urinary glycosaminoglycans. It lists 0 analyses. The presence of multiple outcomes raises a general multiplicity issue: evaluating several outcomes or comparisons can increase the chance of at least one apparently unusual result if no adjustment or prespecified hierarchy is used. The registry does not report a multiplicity strategy or clarify how the listed outcomes relate to a testing hierarchy.
The planning assumptions described in the record concern a general sample-size illustration based on an observed effect, equal allocation, a two-sided significance level of 0.05, and a normal approximation. Such planning calculations are not observed power and do not establish that the trial was designed to detect a particular effect. The primary outcome is identified as a count-other endpoint, and the record notes that values are missing or not estimable for a two-arm comparison. No sample-size illustration for this outcome is reported. The trial’s own sample-size justification is not reported in the registry record.
For a count endpoint, a two-group comparison may require assumptions about the event distribution, exposure, and variability. General planning methods also depend on the target effect and the chosen type I error and power. Without an appropriate estimate and prespecified assumptions, a planning result should not be reconstructed from group totals alone. No adjusted or recalculated comparative estimate is reported for this endpoint, and the posted group counts should not be mistaken for a statistical test.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures and 5 posted secondary outcomes. It does not report a prespecified hierarchy among the primary, secondary, and exploratory outcomes, or a method for controlling multiplicity across outcomes, dose groups, or time points. In general, when many hypotheses are examined, the chance of a false-positive finding can increase unless the analysis plan accounts for the number and relationship of the tests. This is a general consideration; the registry does not establish which outcomes were formally tested.
The record lists 0 analyses and does not post a comparative statistical analysis for the primary endpoint. It does not report a statistical analysis plan, the planned handling of repeated events, a model for the count data, or whether any interim analyses occurred. Those items are not reported in the registry record. No claim about the presence or absence of analyses outside the registry can be made from this record alone.
The primary outcome identifies an ITT population, but the registry does not explain how that population was defined or how missing outcome information was handled. The number of participants with missing data, reasons for missingness, imputation methods, and sensitivity analyses are not reported in the registry record. In general, missing-data methods matter because conclusions can depend on whether missingness is related to outcomes or group assignment. The posted summaries do not permit that assessment.
The registry also does not report adherence, withdrawals by group, protocol deviations, or the specific denominators used for every safety-term percentage. These omissions limit assessment of how completely the posted results represent the planned population and follow-up.
11. 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 |
|---|---|---|---|
| Control | 0 | 4 | 0.0% |
| Idursulfase IT (1 mg) | 3 | 4 | 75.0% |
| Idursulfase IT (10 mg) | 2 | 4 | 50.0% |
| Idursulfase IT (30 mg) | 2 | 4 | 50.0% |
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 |
|---|---|
| Control | 4 of 4 |
| Idursulfase IT (1 mg) | 4 of 4 |
| Idursulfase IT (10 mg) | 4 of 4 |
| Idursulfase IT (30 mg) | 4 of 4 |
Most frequent serious adverse event terms
| Event term | Organ system | Control | Idursulfase IT (1 mg) | Idursulfase IT (10 mg) | Idursulfase IT (30 mg) |
|---|---|---|---|---|---|
| Implant site infection | Infections and infestations | 0 of 4 | 1 of 4 | 0 of 4 | 2 of 4 |
| Device dislocation | Injury, poisoning and procedural complications | 0 of 4 | 1 of 4 | 1 of 4 | 0 of 4 |
| Dehydration | Metabolism and nutrition disorders | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 |
| Vomiting | Gastrointestinal disorders | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 |
| Complication of device insertion | Injury, poisoning and procedural complications | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 |
| Device breakage | Injury, poisoning and procedural complications | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 |
| Device connection issue | Injury, poisoning and procedural complications | 0 of 4 | 0 of 4 | 1 of 4 | 0 of 4 |
| Device failure | Injury, poisoning and procedural complications | 0 of 4 | 0 of 4 | 1 of 4 | 0 of 4 |
| Device malfunction | Injury, poisoning and procedural complications | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 |
| Wound dehiscence | Injury, poisoning and procedural complications | 0 of 4 | 1 of 4 | 0 of 4 | 0 of 4 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Control | Idursulfase IT (1 mg) | Idursulfase IT (10 mg) | Idursulfase IT (30 mg) |
|---|---|---|---|---|---|
| Procedural Pain | Injury, poisoning and procedural complications | 3 of 4 | 4 of 4 | 4 of 4 | 2 of 4 |
| Upper respiratory tract | Infections and infestations | 1 of 4 | 3 of 4 | 3 of 4 | 4 of 4 |
| Vomiting | Gastrointestinal disorders | 1 of 4 | 2 of 4 | 3 of 4 | 1 of 4 |
| Blood Pressure Diastolic Decreased | Investigations | 0 of 4 | 2 of 4 | 3 of 4 | 2 of 4 |
| Blood Pressure Systolic Increased | Investigations | 1 of 4 | 2 of 4 | 2 of 4 | 2 of 4 |
| Otorrhoea | Ear and labyrinth disorders | 0 of 4 | 1 of 4 | 2 of 4 | 2 of 4 |
| Blood Pressure Systolic Decreased | Investigations | 0 of 4 | 1 of 4 | 2 of 4 | 2 of 4 |
| Heart Rate Decreased | Investigations | 1 of 4 | 2 of 4 | 1 of 4 | 1 of 4 |
| Headache | Nervous system disorders | 1 of 4 | 0 of 4 | 3 of 4 | 0 of 4 |
| Pyrexia | General disorders | 0 of 4 | 2 of 4 | 0 of 4 | 2 of 4 |
Serious events with the highest arm-level rate: implant site infection (50.0%), dehydration (25.0%), vomiting (25.0%), device dislocation (25.0%), complication of device insertion (25.0%).
The primary safety outcome is the number of serious adverse events during 6 months: 0 in control, 8 with 1 mg, 3 with 10 mg, and 3 with 30 mg. The primary-outcome record lists 4 participants in each group. These are event totals, not counts of affected participants.
The separate safety summary reports serious adverse events in 0 of 4 control participants, 3 of 4 participants in the 1 mg group, 2 of 4 in the 10 mg group, and 2 of 4 in the 30 mg group. For other adverse events, 4 of 4 participants are listed as affected in each group. A participant-level affected count and an event total should not be substituted for one another: one participant can have more than one event.
The registry lists implant site infection at 50.0%, dehydration at 25.0%, vomiting at 25.0%, device dislocation at 25.0%, complication of device insertion at 25.0%, and device breakage at 25.0% among the top serious terms. The denominator and calculation method for these percentages are not reported in the registry record. Death counts are not reported in the registry record.
These summaries describe reported events; they do not state whether events were attributed to treatment. With small groups and no formal comparative analysis, the figures should not be read as a dose ranking or as evidence that an intervention caused or prevented an event.
12. What the Result Does, and Does Not, Mean
The posted results document serious adverse-event counts and affected-participant counts across the control and three intrathecal dose groups during the reported safety period. The primary outcome lists 0, 8, 3, and 3 events for control, 1 mg, 10 mg, and 30 mg, respectively. The separate safety data list 0 of 4, 3 of 4, 2 of 4, and 2 of 4 participants with serious adverse events. These are different summaries of safety experience, and both should be considered in their own terms.
The results do not establish a causal relationship between the study intervention and any event. Nor do they show that one dose is safer or less safe than another. There is no formal comparison, uncertainty interval, or event-level detail in the registry record to support those conclusions. The listed counts are useful as descriptive observations from this trial, but they are not a definitive estimate of event risk.
The study was intended to obtain safety and exposure information, as well as secondary and exploratory measures, for use in designing subsequent clinical trials. The record lists five secondary outcomes, including measures of glycosaminoglycans and idursulfase concentrations. The presence of these outcomes does not establish an effect on them; their results and analyses are not described in the primary safety summaries.
In general, an early-phase safety and dose-ranging study can contribute information about observed events and the feasibility of studying different doses. It cannot necessarily answer broader questions about longer-term outcomes, effectiveness, or uncommon harms, particularly when group sizes are small. Those general limitations apply to interpretation of descriptive data and do not imply a particular clinical conclusion.
The record does not report a trial-specific sample-size justification, a formal hypothesis-testing plan, or an analysis of comparative effects. It also does not report event attribution, missing-data handling, or detailed follow-up by group. Accordingly, the result is best read as a registry account of observed event counts and participant counts, not as proof of benefit, absence of benefit, or a definitive safety comparison.
13. Why This Trial Matters Statistically
This study illustrates a statistical challenge common to early-phase trials: the outcome of interest may be an event count, while readers also need to know how many participants were affected. Those measures can differ when participants experience repeated events. The registry reports both kinds of summaries for serious adverse events, making it important to distinguish event totals from affected-participant counts rather than treating them as interchangeable.
The trial also includes a control group and three dose groups, but the registry does not report a formal comparison among them. Descriptive counts can help characterize what was observed, yet they do not quantify the uncertainty around a contrast or account for differences in exposure or recurrence. This is particularly relevant when group sizes are small. General statistical reasoning cautions against treating an ordered set of dose labels and event totals as evidence of a dose-response relationship without an appropriate analysis.
Another statistical issue is the presence of multiple outcomes. The record lists primary, secondary, and exploratory measures, but does not report a multiplicity strategy or testing hierarchy. A clear hierarchy can help readers distinguish confirmatory questions from supportive or exploratory ones. Without that information, the status of any individual outcome as a formal test is uncertain.
The registry describes the study’s purpose as collecting safety and exposure data to inform subsequent trials. That makes transparent reporting of the outcome definitions, analysis populations, missing data, and event handling especially important: these details can inform later study design. In this record, some of those methods are not reported. The posted summaries nevertheless show why early-phase safety results require careful separation of descriptive evidence from comparative inference.
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 primary outcome is a count of serious adverse events, but the registry does not report event-level data, recurrence patterns, timing, exposure-adjusted rates, or the method used to classify and adjudicate seriousness. It also does not report whether events were considered related to intrathecal idursulfase, the delivery device, or background treatment. These absences prevent a more detailed interpretation of the event totals.
The group summaries are small, with 4 participants listed in each group for the primary outcome. Such summaries provide limited precision, and a small number of participants can have a substantial influence on observed counts. No confidence intervals or formal group comparisons are reported. The registry also does not state whether the study was intended or powered to compare serious adverse events across groups.
The control group is described as untreated, while the overall study description concerns intrathecal treatment in conjunction with intravenous Elaprase. The registry record does not provide enough detail to determine the control group’s background treatment or to define all differences in care between groups. The exact randomization process and allocation concealment are also not reported.
Outcome completeness and analysis choices are difficult to assess because missing-data handling, withdrawals, adherence, protocol deviations, and the detailed ITT population definition are not reported. The registry lists 0 analyses and does not state a multiplicity plan. In addition, the denominator and derivation for the listed serious-event term percentages are not reported in the registry record. The reported values should therefore be interpreted as registry summaries, not as a complete account of all trial methods or event-level evidence.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Safety and Dose Ranging Study of Idursulfase (Intrathecal) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Hunter Syndrome Who Have Central Nervous System Involvement and Are Receiving Treatment With Elaprase® — NCT00920647.
- Registry record last updated 2021-06-28; status last verified 2021-06.
- Results first posted 2014-05-16.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
The registry describes NCT00920647 as a completed Phase I/II randomized, unmasked, parallel study in pediatric patients with Hunter syndrome. It lists 16 enrolled participants and an intervention schedule of monthly intrathecal idursulfase at 1 mg, 10 mg, or 30 mg, compared with a control group described as untreated.
The primary outcome is the number of serious adverse events over 6 months in the identified ITT population. The posted counts are 0 in control, 8 in the 1 mg group, 3 in the 10 mg group, and 3 in the 30 mg group. The separate safety summary reports serious events in 0 of 4, 3 of 4, 2 of 4, and 2 of 4 participants, respectively. No formal comparative analysis is reported.
The study description says its aim was to obtain safety and exposure information and secondary and exploratory outcomes to inform subsequent trials. The record lists 11 outcome measures, 5 posted secondary outcomes, and 0 analyses. Important details—including the statistical analysis plan, missing-data methods, and formal between-group estimates—are not reported in the registry record.