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 Study Of Pharmacokinetics, Whole Body And Organ Dosimetry, And Biodistribution Of Fission-Derived Iodine I 131 Tositumomab (BEXXAR®) For Patients With Previously Untreated Or Relapsed Follicular Or Transformed Non-Hodgkin's Lymphoma (NCT00315731), a na phase 1 study. The primary outcome is Area Under the Curve (AUC) at 0 to 120, 0 to 168, and 0 to Infinity Hours.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00315731 |
| Phase | Phase 1 |
| Condition | Lymphoma, Follicular |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 15 |
| Arms in the primary outcome | n/a |
| Lead sponsor | GlaxoSmithKline |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with previously untreated or relapsed follicular or transformed follicular non-Hodgkin's lymphoma. The primary pharmacokinetic assessment population is described as participants evaluable for pharmacokinetic assessment under protocol criteria. The registry record does not report how many participants met those criteria, or provide a further description of the criteria.
Intervention
Participants received tositumomab and iodine I 131 tositumomab. The described procedure began with unlabeled tositumomab followed by a dosimetric infusion of fission-derived iodine I 131 tositumomab. Dosimetry information was then used to calculate a patient-specific activity for the subsequent treatment intended to deliver a total body dose of 75 cGy.
Comparator
There was no separate comparator group. The study was single-group, with allocation recorded as not applicable. It therefore does not provide a randomized, like-for-like contrast between treatments or between treatment and a control condition.
Primary question
The primary question was how much iodine I 131 tositumomab was present in the blood over time after the dosimetric infusion, as measured by area under the concentration-time curve from time 0 to 120 hours, 0 to 168 hours, and 0 to infinity hours. The record also describes study aims concerning pharmacokinetics, dosimetry, and radionuclide biodistribution. Numerical primary endpoint estimates are not reported in the registry record.
This study is best understood as an investigation of drug disposition and radiation dosimetry, not as a controlled comparison of clinical benefit. Blood sampling and imaging were intended to characterize how the radiolabeled antibody moved through the body and how radiation was distributed. The subsequent patient-specific activity was calculated using dosimetry information and participant weight. The record lists response and safety follow-up as additional study objectives, but does not report numerical response outcomes in the information available for this analysis. Consequently, the primary clinical question concerns measurement and characterization; the record does not establish a comparative effect on lymphoma outcomes.
3. Trial Design
The registry record describes a Phase 1, multi-center, single-group study with no masking and no randomized allocation. Enrollment was 15. The study status is completed; the recorded start date is 2003-03-31 and the primary completion date is 2006-12-04. The sponsor was GlaxoSmithKline. These design features describe the conduct recorded in the registry, but do not establish how many enrolled participants contributed data to each outcome analysis.
Participants were to receive a dosimetric dose of fission-derived iodine I 131 tositumomab following an infusion of 450 mg of unlabeled tositumomab. The brief summary describes a standard 5 mCi dosimetric dose. Blood samples were planned at 12 timepoints over the first 7 days after this dose for pharmacokinetic assessment. Whole-body gamma camera imaging was planned on six days following the dosimetric dose, with organ and tumor dosimetry generated from counts in specified regions. An independent review panel was to examine scans for radionuclide biodistribution.
Dosimetry information from three of the six imaging timepoints, together with participant weight, was used to calculate a patient-specific iodine I 131 activity intended to deliver a total body dose of 75 cGy. The brief summary describes a subsequent infusion of 450 mg of unlabeled tositumomab followed by patient-specific tellurium-derived iodine I 131 tositumomab at 35 mg. The design therefore combines pharmacokinetic sampling and imaging with individualized activity calculation rather than assigning participants to different randomized treatment arms.
The planned follow-up included close safety monitoring after treatment and assessment of response and safety at 3, 6, and 12 months during the first year, annually thereafter up to five years, and annual safety and outcome information up to 10 years. Details of adherence, actual follow-up completeness, departures from the planned schedule, and the number assessed at each visit 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: Blood pharmacokinetics (the primary objective), biodistribution, and organ dosimetry following a dosimetric dose of tositumomab and fission-derived iodine I-131 tositumomab in this study were compared with results following a dosimetric dose of tositumomab and tellurium-derived iodine I-131 tositumomab in a historical control group (NCT00996996).
Overall Study
| Stage | Tositumomab and Fission-derived Iodine I-131 Tositumomab |
|---|---|
| STARTED | 15 |
| COMPLETED | 9 |
| NOT COMPLETED | 6 |
Reasons for not completing this period:
| Reason | Tositumomab and Fission-derived Iodine I-131 Tositumomab |
|---|---|
| Lost to Follow-up | 1 |
| Death | 5 |
Analysis population for the primary outcome, as defined in the registry: All participants considered as evaluable for pharmacokinetic assessment per protocol criteria.
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 | Tositumomab and Fission-derived Iodine I-131 Tositumomab |
|---|---|---|
| Participants analysed | 15 | |
| Age, Continuous | Years | 58.1 (SD 12.9) |
| Sex: Female, Male: Female | Participants | 5 |
| Sex: Female, Male: Male | Participants | 10 |
| Race/Ethnicity, Customized: Caucasian | participants | 15 |
6. Primary Endpoint
The registry lists the primary outcome as Area Under the Curve (AUC) at 0 to 120, 0 to 168, and 0 to Infinity Hours, measured over 0-120, 0-168, and 0-infinity hours from dosimetric dose (given only once on Day 0).
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | %ID.h/mL |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is area under the concentration-time curve, or AUC, for iodine I 131 tositumomab in blood. It is described over time 0 to 120 hours, time 0 to 168 hours, and time 0 to infinity hours, with the last interval extrapolated. The stated unit is %ID.h/mL, where %ID/mL represents the percentage of the injected dose per milliliter of blood. AUC combines concentration and time into a measure of overall systemic exposure during the specified interval.
As a general statistical and pharmacokinetic concept, concentrations measured at successive times can be considered as a curve. The area under that curve reflects both the level of measured concentration and how long it persists. This can summarize drug exposure more fully than a measurement at a single sampling time, which may capture only one point in the concentration profile. The shorter stated intervals characterize exposure over defined observed periods; the extrapolated interval attempts to represent exposure beyond the observed sampling period, subject to the assumptions used for extrapolation.
The endpoint is reported as a geometric mean with a 95% confidence interval. A geometric mean is a way to summarize positive measurements when values are naturally considered on a multiplicative scale. A confidence interval conveys uncertainty around an estimated population value; it is not a range that contains every participant's measurement. The registry record describes the endpoint and its intended population, but numerical estimates and confidence limits are not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registered primary outcome is an estimate of systemic pharmacokinetic exposure after the dosimetric dose. The study intended to estimate AUC across three specified intervals, and to express those estimates as geometric means with 95% confidence intervals. Those endpoint definitions explain what the analysis was designed to measure; they do not reveal the observed AUC values. Numerical estimates, interval limits, and the number of participants included in each endpoint calculation are not reported in the registry record.
This distinction matters because a study objective is not itself a result. The registry describes the collection of blood samples, the time intervals for AUC, and the pharmacokinetic population as participants meeting protocol criteria. It does not provide the corresponding observed concentrations or a numerical summary of exposure. Therefore, no direction, magnitude, or precision of the primary pharmacokinetic findings can be stated from this record.
The study was single-group and had no comparator. Its observed pharmacokinetic or dosimetry measurements, if reported elsewhere, would describe participants receiving the study regimen under the study conditions. They would not by themselves establish how those measurements compare with a different regimen, an untreated group, or a population enrolled under different eligibility criteria. There is no randomized contrast in this record from which to infer a between-group treatment effect.
Other listed outcomes include AUC over additional intervals, maximum concentration, mean residence time, absorbed dose in source and target organs, expected distribution of radioactivity, and response categories. The record names these outcomes but does not include numerical results for them in the information available for this analysis. It also lists serious adverse event information. Such safety counts have a different purpose from pharmacokinetic estimates and should not be treated as evidence of a comparative effect, particularly in a study without a control group.
Confidence intervals are intended to communicate uncertainty in estimates. As a general statistical explanation, a narrower interval indicates greater precision under the analysis assumptions, while a wider interval indicates less precision. An interval does not correct for limitations such as selection into the evaluable population, missing measurements, or lack of a comparator. In this case, the actual interval estimates are not reported in the registry record, so their width and the precision of the primary estimates cannot be assessed.
The registry record reports enrollment of 15, but enrollment is not necessarily the same as the number analyzed for every outcome. The primary endpoint is defined for participants considered evaluable for pharmacokinetic assessment under protocol criteria, and the number meeting those criteria is not reported. It would therefore be inappropriate to assume that every enrolled participant contributed complete data to every pharmacokinetic, imaging, response, or safety analysis.
Overall, the posted information supports a description of the study question, dosing and measurement plan, and selected safety counts. It does not support conclusions about the magnitude or precision of the primary pharmacokinetic estimates, the observed organ dosimetry, or response outcomes. Nor does it permit a controlled assessment of treatment effects. Those boundaries should guide any interpretation of the record.
9. Statistical Methods Explained
The primary endpoint is pharmacokinetic AUC for iodine I 131 tositumomab after the dosimetric infusion. Pharmacokinetics describes how a substance moves through the body over time. In this study, the registry describes blood sampling at 12 timepoints over the first 7 days after administration. The concentration measurements at successive sampling times can be used to characterize a concentration-time profile. AUC reduces that profile to a summary of exposure over a specified interval.
What does AUC represent?
As a general concept, AUC incorporates both concentration and duration. A high concentration that persists and a lower concentration that persists longer can contribute differently to total exposure; the complete time course is relevant. The registry specifies AUC from time 0 to 120 hours, from time 0 to 168 hours, and from time 0 to infinity hours. The infinity interval is described as extrapolated, so it extends beyond the directly observed period by using an estimate of the remaining exposure. The record does not report the exact calculation procedure or the extrapolation assumptions.
The endpoint unit, %ID.h/mL, combines the percentage of injected dose per milliliter of blood with time. The registry explains %ID/mL as the percentage of injected dose per milliliter of blood. AUC is therefore a measure of exposure across time, not a direct measure of clinical response, tumor change, or radiation absorbed by a particular organ.
Why report a geometric mean?
The primary endpoint is specified as a geometric mean. As a general statistical concept, the geometric mean summarizes positive values on a multiplicative scale and can be useful when measurements are skewed or when relative rather than additive variation is meaningful. It differs from an arithmetic mean, which summarizes values on an additive scale. The registry does not state why this summary was selected or report the underlying participant-level measurements, so the distribution of the observed AUC values cannot be assessed from the record.
How should the confidence interval be read?
The endpoint is accompanied by a 95% confidence interval. As a general explanation, a confidence interval presents a range of values compatible with the estimate under the statistical model and repeated-sampling framework used for the analysis. It communicates uncertainty in the estimated mean; it does not describe the full range of individual participant values or imply that a particular proportion of participants had measurements inside the interval. The numerical interval limits are not reported in the registry record, so the precision of the primary estimate cannot be judged.
What role did imaging and dosimetry play?
The study also planned whole-body gamma camera imaging on six days after the dosimetric dose. Organ and tumor dosimetry were to be generated from gamma camera counts for specified regions, and scans were to be examined by an independent review panel for biodistribution. These measures concern where radioactivity is distributed and the estimated absorbed dose in source and target organs. They are related to, but distinct from, the blood concentration AUC endpoint. The registry record does not provide numerical organ dose estimates or detailed image-analysis procedures.
Dosimetry from three of the six imaging timepoints and participant weight were used to calculate a patient-specific activity intended to deliver a total body dose of 75 cGy. This is an individualized dosing process described in the study summary. It does not imply that every participant received the same activity, and the record does not provide the calculated activity values. The stated subsequent treatment was tellurium-derived iodine I 131 tositumomab at 35 mg following 450 mg of unlabeled tositumomab.
What can be inferred from a single-group design?
As a general design principle, a single-group study can describe measurements observed among people who received a specified regimen. Without a concurrent comparator, it cannot isolate a treatment contrast from other explanations or establish how outcomes would have differed under another intervention. This is particularly relevant to response and safety outcomes, which can be influenced by participant characteristics, disease course, follow-up, and other care. The record identifies no randomized allocation and no separate control arm.
The primary endpoint population is described as participants evaluable for pharmacokinetic assessment under protocol criteria. An analysis restricted to evaluable participants can differ from an analysis of all enrolled participants if measurements are missing or participants do not meet assessment criteria. The registry does not report the criteria, the number evaluable, or the handling of missing measurements. Thus, the size and composition of the analyzed population cannot be determined from the record.
The registry lists multiple pharmacokinetic, dosimetry, biodistribution, and response outcomes. It does not report a complete statistical analysis plan, methods for multiplicity control, the handling of missing data, or interim analyses. No inference about those methods should be made from the endpoint descriptions alone. The numerical primary endpoint results are also not reported in the registry record, preventing assessment of the point estimates, their confidence intervals, and consistency across the specified time intervals.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a range of outcomes covering pharmacokinetics, dosimetry, biodistribution, and response. It identifies a primary AUC endpoint over three time intervals, and lists other outcomes including maximum concentration, mean residence time, absorbed dose in source and target organs, expected distribution of radioactivity, and response categories. Because several outcomes and intervals are listed, interpretation would ordinarily benefit from knowing which analyses were designated as primary or secondary, how conclusions were to be drawn across multiple outcomes, and whether any adjustment for multiple testing was planned. Those details are not reported in the registry record.
The number of outcome measures is listed as 16, and the record lists 4 analyses. These counts do not, on their own, explain how the analyses relate to individual outcomes, whether each was prespecified, or whether any multiplicity procedure was used. The statistical analysis plan, including any interim analyses, is not reported in the registry record.
The primary pharmacokinetic population is defined as participants evaluable under protocol criteria. The criteria themselves, the number of participants meeting them, and the reasons for any exclusions are not reported in the registry record. Enrollment was 15, but that does not establish the analysis population for each endpoint. The record also does not describe how incomplete blood sampling, unavailable imaging, or missing follow-up data were handled. Missing-data methods and endpoint-specific denominators are not reported in the registry record.
These omissions limit assessment of whether the reported analyses, if available elsewhere, represent all enrolled participants or only an evaluable subset. They also prevent evaluation of how outcome multiplicity and incomplete data may affect the certainty of conclusions. No particular analysis choice should be assumed in the absence of a reported method.
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 |
|---|---|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | 4 | 15 | 26.7% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tositumomab and Fission-derived Iodine I-131 Tositumomab | 15 of 15 |
Most frequent serious adverse event terms
| Event term | Organ system | Tositumomab and Fission-derived Iodine I-131 Tositumomab |
|---|---|---|
| Pyrexia | General disorders | 1 of 15 |
| Squamous cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 15 |
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 15 |
| Squamous cell carcinoma of oral cavity | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 15 |
| Acute lymphocytic leukemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 15 |
| Basal cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 15 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tositumomab and Fission-derived Iodine I-131 Tositumomab |
|---|---|---|
| Absolute neutrophil count (calc) <1000 cells/millimeter^3 | Investigations | 8 of 15 |
| Neutropenia | Blood and lymphatic system disorders | 7 of 15 |
| Fatigue | General disorders | 6 of 15 |
| Thrombocytopenia | Blood and lymphatic system disorders | 6 of 15 |
| Nausea | Gastrointestinal disorders | 6 of 15 |
| Pyrexia | General disorders | 5 of 15 |
| White Blood Cell count <2000 cells/millimeter^3 | Investigations | 5 of 15 |
| Chills | General disorders | 4 of 15 |
| Platelets <50000 cells/millimeter^3 | Investigations | 4 of 15 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 3 of 15 |
Serious events with the highest arm-level rate: pyrexia (6.7%), squamous cell carcinoma (6.7%), lung neoplasm malignant (6.7%), squamous cell carcinoma of oral cavity (6.7%), acute lymphocytic leukemia (6.7%).
The registry reports 15 participants at risk for other adverse events and 15 participants affected. For serious adverse events, 15 participants were at risk and 4 were affected. These are participant counts in the study group; they are not a comparison with another treatment or a control group. The record lists serious adverse event terms including pyrexia, squamous cell carcinoma, lung neoplasm malignant, squamous cell carcinoma of oral cavity, acute lymphocytic leukemia, and basal cell carcinoma, each reported as 6.7%.
These entries should be read as registry safety summaries, not as proof that the study treatment caused a particular event. A single-group record cannot provide a controlled comparison of event frequency, and the listed terms do not by themselves establish timing, severity details, recurrence, or causal attribution. The registry record does not report deaths in the displayed safety information.
Serious adverse event counts and other adverse event counts are distinct categories and should not be combined. The affected-participant counts also do not describe the number of events per participant. Additional details about event definitions, follow-up completeness, attribution procedures, and the analysis population are not reported in the registry record. The available figures therefore describe recorded safety events in this study group, with limits on causal and comparative interpretation.
12. What the Result Does, and Does Not, Mean
The study record describes a Phase 1 investigation designed to characterize pharmacokinetics, whole-body and organ dosimetry, and biodistribution of iodine I 131 tositumomab in patients with follicular or transformed follicular non-Hodgkin's lymphoma. Its primary outcome is AUC across specified intervals after a dosimetric dose. The study also planned imaging, individualized activity calculation, safety monitoring, and response follow-up. These features establish the scientific focus and measurement plan.
The numerical primary outcome estimates are not reported in the registry record. Consequently, the size of the observed AUC, its confidence interval, and the precision of the estimate cannot be described. Numerical results for the listed dosimetry and response outcomes are also not reported in the record. The methods and outcome definitions should not be mistaken for findings.
The study included a single group and no comparator. Its design can describe observations among those who received the regimen, but it does not provide a randomized comparison that separates treatment differences from other factors. The results therefore cannot establish a comparative effect on response, safety, or any other outcome. The registry's safety counts describe recorded events in the study group and do not establish that treatment caused those events.
As a general statistical point, an estimate is most informative when accompanied by a clear analysis population, a measure of uncertainty, and enough design information to understand how the data were collected and analyzed. Here, the record specifies the intended primary population as participants evaluable under protocol criteria, but does not report the number meeting those criteria or the missing-data procedures. The implications of those unknowns cannot be quantified.
The appropriate conclusion is limited: the registry documents a study plan and selected safety counts for a single-group pharmacokinetic and dosimetry investigation. It does not report enough numerical primary outcome information to assess observed systemic exposure or its precision, and it does not support a controlled treatment-effect conclusion.
13. Why This Trial Matters Statistically
This study is statistically notable for linking pharmacokinetic measurement with individualized dosimetry. Blood concentration sampling was intended to characterize systemic exposure, while gamma camera images were used to assess radionuclide distribution and support calculation of a patient-specific activity. The two measurement types answer related but distinct questions: blood AUC summarizes exposure over time, while dosimetry concerns estimated radiation absorbed in organs or other targets.
The design also illustrates why the analysis population matters. The registry defines the primary pharmacokinetic population by protocol evaluability, rather than simply stating that all enrolled participants were analyzed. With enrollment of 15, an endpoint-specific denominator and transparent criteria would be important for understanding how much data contributed to the estimate. The record does not provide those details.
As a general methodological point, individualized dosing may require careful separation of the dose-calculation process from outcome assessment. The registry describes how dosimetry information and weight informed the activity intended to deliver a total body dose of 75 cGy. It does not provide enough numerical results or procedural detail to assess variability in calculated activities, the precision of dose estimates, or how those features related to pharmacokinetic outcomes.
The single-group design sets a clear boundary on interpretation. It can support descriptive characterization, but cannot supply a randomized comparison. The absence of numerical primary results in the registry record adds a further boundary: even descriptive exposure estimates and their precision cannot be evaluated. Together, these features make the study useful as a documented measurement framework while limiting conclusions about observed outcomes and comparative effects.
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 registry record does not report numerical values for the primary AUC endpoint, including its geometric mean estimates and 95% confidence intervals. As a result, neither the magnitude nor precision of the primary pharmacokinetic findings can be assessed. Numerical findings for the listed secondary pharmacokinetic, dosimetry, biodistribution, and response outcomes are also not reported in the record.
The study was single-group, with no randomized allocation or separate comparator. This prevents a like-for-like comparison and limits causal interpretation of response and safety observations. The study's enrollment was 15, but the record does not provide endpoint-specific analysis populations. The primary endpoint population is described as participants evaluable for pharmacokinetic assessment under protocol criteria; those criteria and the number meeting them are not reported.
The record describes planned sampling and imaging schedules but does not report completeness of measurements, the handling of missing data, or reasons participants may have been unevaluable. It also does not report detailed statistical methods for AUC calculation, extrapolation to infinity, confidence interval construction, multiplicity handling, or interim analyses. These are not details that can be inferred from the endpoint labels.
Safety information is limited to the reported participant counts and listed serious adverse event terms. The record does not supply fuller details on event timing, attribution, recurrence, or the completeness of follow-up. The displayed death count is not reported in the registry record. These limitations restrict interpretation to the study design and the selected recorded safety summaries, rather than broader conclusions about causation or comparative risk.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study Of Pharmacokinetics, Whole Body And Organ Dosimetry, And Biodistribution Of Fission-Derived Iodine I 131 Tositumomab (BEXXAR®) For Patients With Previously Untreated Or Relapsed Follicular Or Transformed Non-Hodgkin's Lymphoma — NCT00315731.
- Registry record last updated 2017-07-11; status last verified 2017-06.
- Results first posted 2012-04-23.
- 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
This is a completed Phase 1, multi-center, single-group study sponsored by GlaxoSmithKline, with enrollment of 15 and no masking. It investigated pharmacokinetics, dosimetry, and biodistribution of iodine I 131 tositumomab in patients with previously untreated or relapsed follicular or transformed follicular non-Hodgkin's lymphoma.
The primary endpoint was AUC from time 0 to 120 hours, 0 to 168 hours, and 0 to infinity hours after a dosimetric dose. Blood sampling, gamma camera imaging, and patient-specific activity calculation were part of the described study approach. Numerical primary endpoint results and the number included in the pharmacokinetic analysis are not reported in the registry record. The record reports 4 participants affected by serious adverse events among 15 at risk, with no comparator group for interpreting event frequencies.