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 36-month Special Drug Use Surveillance on Frequency of Bone Fractures With Sodium Risedronate 75 mg Tablets (NCT02106442), a registered phase not stated study. The primary outcome is Cumulative Percentage of Participants With New or Worsening Vertebral Body Fractures.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02106442 |
| Phase | Phase not stated |
| Condition | Osteoporosis |
| Allocation | Not Stated |
| Design model | Not Stated |
| Masking | Not Stated |
| Enrollment | 579 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Takeda |
| Results posted | Yes |
2. Clinical Question
Population
People with osteoporosis receiving routine medical care were included in a special drug use surveillance. The record lists enrollment of 579 participants. For the primary endpoint, the assessment population was narrower: participants had to complete the survey and have evaluable vertebral fracture data at baseline and post-baseline time points. The number analyzed for that endpoint is not reported in the registry record.
Intervention
The intervention was sodium risedronate 75 mg tablets. The regimen described was oral administration once monthly after waking, with approximately 180 mL of water. The record describes treatment as part of routine medical care rather than as a treatment assigned by a randomized study protocol.
Comparator
No comparator group is listed. The record does not state an allocation method, and it does not describe a randomized comparison. The results therefore cannot be read as a like-for-like comparison between sodium risedronate and another treatment or a control condition.
Primary question
The primary outcome is the cumulative percentage of participants with new or worsening vertebral body fractures from baseline up to Month 36. The surveillance also lists non-vertebral and femur fractures, bone mineral density measures, and bone metabolism markers as secondary outcomes. Numerical results for these outcomes are not reported in the registry record, so the primary question cannot be answered from the posted outcome data.
3. Trial Design
This is a completed special drug use surveillance of sodium risedronate 75 mg in osteoporosis patients receiving routine medical care. The record lists Takeda as the sponsor, enrollment of 579, a start date of 2013-05-13, and a primary completion date of 2018-04-30. The planned observation period for the primary outcome runs from baseline up to Month 36.
The record describes one treatment group and no comparator. Allocation is not stated, and this is not a randomized comparison. The drug regimen is described as one oral 75 mg dose once monthly after waking, taken with a sufficient volume of water, approximately 180 mL. The record does not give further details about treatment adherence, changes in treatment, or concomitant care.
The primary outcome is a cumulative percentage of participants with new or worsening vertebral body fractures. The description specifies data collection between baseline and Month 36, with reported assessment times at baseline and Months 6, 12, 18, 24, 30, and 36. The primary assessment population consists of survey completers with evaluable vertebral fracture data at baseline and post-baseline times. The number analyzed at each assessment time is not reported in the registry record.
The registry record lists 15 outcome measures, including fracture outcomes, bone mineral density changes at several sites, and changes in bone metabolism markers. It reports no analyses. The protocol details, statistical analysis plan, and justification for the enrollment target are not reported in the registry record. Completion status alone does not establish that every planned assessment was available or that every participant contributed data through Month 36.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Before assignment: Participants with a historical diagnosis of osteoporosis were enrolled. Participants received interventions as part of routine medical care.
Overall Study
| Stage | Sodium Risedronate 75 mg |
|---|---|
| STARTED | 579 |
| COMPLETED | 542 |
| NOT COMPLETED | 37 |
Reasons for not completing this period:
| Reason | Sodium Risedronate 75 mg |
|---|---|
| Case Report Forms Uncollected | 7 |
| Protocol Deviation | 30 |
Analysis population for the primary outcome, as defined in the registry: Vertebral fractures assessment population; The vertebral fractures assessment population was defined as participants who completed the survey and had evaluable vertebral fractures data at baseline and post-baseline time points. Number analyzed is the number of participants who were evaluable at each time point.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
Population: Safety Analysis Set, The safety analysis set was defined as all participants who completed the survey.
| Characteristic | Unit | Sodium Risedronate 75 mg |
|---|---|---|
| Participants analysed | 542 | |
| Age, Continuous | Years | 75.9 (SD 8.0) |
| Sex: Female, Male: Female | Participants | 479 |
| Sex: Female, Male: Male | Participants | 63 |
| Race and Ethnicity Not Collected | Participants | — |
| Region of Enrollment: Japan | Participants | 542 |
| Height | Centimeters (cm) | 148.65 (SD 7.88) |
| Weight | Kilograms (kg) | 50.37 (SD 11.79) |
| BMI | Kg/meters (m)^2 | 22.81 (SD 4.81) |
| Osteoporosis Class: Primary Osteoporosis | Participants | 481 |
| Osteoporosis Class: Secondary Osteoporosis | Participants | 28 |
| Osteoporosis Class: Unknown | Participants | 33 |
| Duration of Diagnosis of Osteoporosis | Years | 1.5 (SD 2.8) |
| Predisposition to Hypersensitivity: Had Predisposition to Hypersensitivity | Participants | 32 |
| Predisposition to Hypersensitivity: Had No Predisposition to Hypersensitivity | Participants | 457 |
| Predisposition to Hypersensitivity: Unknown | Participants | 53 |
| Medical Complications: Had Medical Complications | Participants | 453 |
| Medical Complications: Had No Medical Complications | Participants | 89 |
| Medical History, Excluding History of Fracture: Had Medical History | Participants | 111 |
| Medical History, Excluding History of Fracture: Had No Medical History | Participants | 397 |
| Medical History, Excluding History of Fracture: Unknown | Participants | 34 |
| Fracture Risk Factor: Medical History of Fracture: Had Medical History | Participants | 305 |
| Fracture Risk Factor: Medical History of Fracture: Had No Medical History | Participants | 212 |
| Fracture Risk Factor: Medical History of Fracture: Unknown | Participants | 25 |
| Fracture Risk Factor: History of Steroid Use, Excluding Steroids for External Use: Had History of Steroid Use | Participants | 35 |
| Fracture Risk Factor: History of Steroid Use, Excluding Steroids for External Use: Had No History of Steroid Use | Participants | 477 |
| Fracture Risk Factor: History of Steroid Use, Excluding Steroids for External Use: Unknown | Participants | 30 |
6. Primary Endpoint
The registry lists the primary outcome as Cumulative Percentage of Participants With New or Worsening Vertebral Body Fractures, measured over From baseline up to Month 36.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | 95% Confidence Interval |
| Unit | Percentage of Participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the cumulative percentage of participants with new or worsening vertebral body fractures from baseline up to Month 36. It is a binary outcome at the participant level: a participant either meets the fracture outcome definition during the specified follow-up or does not. The registry record also describes assessments at baseline and Months 6, 12, 18, 24, 30, and 36, but the precise operational definitions used to classify a new or worsening fracture are not reported in the registry record.
A cumulative percentage expresses how many participants in the relevant assessment population experienced the event over the stated follow-up. In general, this type of endpoint is used to communicate the proportion of an observed group with an event over a defined period. It does not, on its own, show when events occurred, compare event rates between treatment groups, or establish why an event occurred.
The registry specifies a 95% confidence interval as the measure of uncertainty for the endpoint, but numerical endpoint estimates and confidence limits are not reported in the registry record. The endpoint population requires completion of the survey and evaluable vertebral fracture data at baseline and post-baseline visits. That restriction matters because the resulting percentage pertains to participants meeting those assessment requirements, not automatically to all enrolled participants.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the clinical question and the intended observation period, but it does not report the primary endpoint estimate or its 95% confidence interval. Consequently, the frequency of new or worsening vertebral fractures in the assessment population cannot be quantified from the posted results. The record also does not report the number analyzed at each time point, so the size of the group contributing to each cumulative estimate is unknown.
The study has a single listed treatment group and no comparator. Its outcome data, even if available, would describe events observed during surveillance among people receiving sodium risedronate in routine medical care. Without a comparison group, an observed proportion could not by itself separate treatment-associated outcomes from the background occurrence of fractures or other influences on participants' health. Allocation is not stated, and the record does not describe random assignment.
The primary endpoint is cumulative over follow-up, rather than a comparison of event counts between randomized groups. In general, a cumulative proportion depends on the definition of the assessment population and on whether participants have sufficient follow-up and outcome assessments. Here, the record defines the primary assessment population as survey completers with evaluable baseline and post-baseline vertebral fracture data. The number of participants satisfying this definition is not reported in the registry record.
The registry lists a 95% confidence interval for the primary outcome, but no estimate or interval is posted. In general, a confidence interval describes the precision of an estimated quantity under the assumptions of the statistical method used. Its width depends on factors including the amount of available information and the number of observed events. Without the numerical interval and analyzed population, precision cannot be assessed. A point estimate without uncertainty would also leave the reliability of the estimate unclear; neither is available for this endpoint.
Other outcomes listed include non-vertebral and femur fractures, percent changes in bone mineral density at lumbar spine, femur neck, total proximal femur, and radius, and changes in serum NTX and TRACP-5b. Their numerical findings are not reported in the registry record. They therefore cannot be used to fill the gap in the primary result or to provide a complete account of the surveillance findings.
The safety record lists 4 serious adverse event reports among 542 at risk, 7 reports in the other adverse-event category among 542 at risk, and 0 deaths. Serious-event terms listed include Toothache, Osteonecrosis, Femur fracture, and Hospitalisation, each reported as 0.2%. These figures are descriptive. The registry record does not provide a control group or the information needed to attribute an event to the drug. A zero death count in the listed group is not evidence that the risk of death is absent.
Overall, the registry describes a completed surveillance with a planned 36-month fracture outcome, but the posted outcome data do not include the numerical primary result. Conclusions about the observed fracture percentage, its precision, and how it varied over follow-up are therefore not possible from the registry record.
9. Statistical Methods Explained
The registry record identifies a percentage outcome and a 95% confidence interval for the primary endpoint. It does not report the numerical estimate, confidence limits, analysis details, or a statistical analysis plan. The explanations below distinguish general statistical concepts from methods specifically documented for this surveillance.
What does a cumulative percentage represent?
In general, a cumulative percentage is the proportion of a defined group that has experienced an event by a specified point or over a specified period. For this endpoint, the event is a new or worsening vertebral body fracture, and the stated period is baseline up to Month 36. The denominator is essential: the registry defines the primary assessment population as participants who completed the survey and had evaluable vertebral fracture data at baseline and post-baseline times. The number meeting that definition is not reported in the registry record.
The outcome description names baseline and Months 6, 12, 18, 24, 30, and 36 as reporting time points. Repeated assessments can describe how cumulative event occurrence develops during follow-up, but interpreting each time point requires knowing how the analysis handled participants with incomplete follow-up and whether the assessment group changed over time. Those details are not reported in the registry record. It is therefore not possible to determine from the record whether all time-point estimates used a consistent denominator.
What does a 95% confidence interval convey?
In general, a confidence interval gives a range of values compatible with an estimate under the statistical model and its assumptions. It communicates precision: narrower intervals indicate more precise estimation, while wider intervals indicate more uncertainty. A confidence interval does not guarantee that the true value lies inside the particular interval, nor does it address every possible source of bias. For example, it cannot by itself correct for incomplete outcome assessment or a nonrepresentative assessment population.
The registry lists a 95% confidence interval for the primary percentage, but its limits are not reported in the registry record. The method used to calculate the interval is also not reported. Without an estimate, interval, event count, and analyzed denominator, neither the magnitude nor the precision of the primary result can be evaluated.
Why does the assessment population matter?
In general, an analysis population defines who contributes to a particular estimate. Requiring completion of the survey and evaluable baseline and post-baseline fracture data may mean that some enrolled participants do not contribute to the primary endpoint. If participants without complete assessments differ from participants with evaluable data, the observed percentage among those assessed may not represent the full enrolled group. This is a general concern about selection and missing outcome data, not evidence that such a difference occurred in this surveillance. The record does not report the number excluded or the reasons for unavailable assessments.
Enrollment is listed as 579, whereas the safety figures use 542 at risk. These counts describe different reported contexts and should not be treated as interchangeable denominators. The primary outcome's analyzed count is not reported in the registry record, and no explanation is given for the relation between enrollment and the safety population.
What can a one-group surveillance estimate establish?
In general, a single-group surveillance can describe outcomes observed in the group under observation. It cannot, without a suitable comparison and adequate control of differences, estimate what would have happened to the same participants under another treatment or no treatment. The registry lists one sodium risedronate group, does not state allocation, and is not a randomized comparison. Any percentage from this design would be a descriptive result for the defined group and observation period, not a randomized estimate of a treatment contrast.
Routine medical care can encompass variation in clinical practice and participant circumstances. The record says participants received sodium risedronate as part of routine care, but it does not describe the consistency of monitoring, adherence, other treatments, or fracture ascertainment procedures. These details affect how directly a descriptive estimate can be interpreted and compared with estimates from other settings.
What do the planning assumptions mean?
The registry's planning illustration is described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of an observed effect. Such a calculation is a planning exercise, not an observed result. The assumptions describe a hypothetical comparison and do not change the fact that the surveillance lists no comparator and is not a randomized comparison. The planning illustration is not observed power. Numerical planning results and a trial-specific sample-size justification are not reported in the registry record.
In general, sample-size planning asks how much information a future study might need under specified assumptions. It does not show that a completed study had a particular probability of detecting an effect after its results are known. Planning conclusions also depend on whether the assumed effect, variability, allocation, and analysis approach are appropriate. Because the primary estimate is not reported, the observed effect underlying the described illustration cannot be examined from the registry record.
What is not documented?
The registry record reports no analyses and does not report a statistical analysis plan, interim analyses, adjustment for covariates, or a method for handling missing data. These absences do not establish which methods were used outside the registry record; they mean the methods cannot be verified from the posted information. No additional calculation can recover a primary estimate from the endpoint description alone.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 15 outcome measures: a primary vertebral fracture outcome and secondary measures covering other fracture outcomes, bone mineral density, and bone metabolism markers. Looking at multiple outcomes can raise a multiplicity issue. In general, the more statistical questions examined, the greater the chance that at least one result may appear unusual by chance if each is assessed separately. Whether and how to address that concern depends on the analysis plan and the role of each outcome. Multiplicity procedures are not reported in the registry record, so it is not possible to determine whether any adjustment or hierarchy was planned.
The record reports no analyses and supplies no numerical outcome findings. It therefore does not support an assessment of which measures were analyzed, whether all planned outcomes were reported, or how results were selected for presentation. The number of outcomes alone does not show that a multiplicity problem occurred; it identifies an issue that would require the analysis plan and results to evaluate.
For the primary outcome, the assessment population is limited to survey completers with evaluable vertebral fracture data at baseline and post-baseline time points. This definition makes completeness relevant to interpretation. In general, missing outcome data can reduce precision and can create bias if availability is related to outcome status or participant characteristics. The record does not report missing-data methods, the extent or pattern of missingness, or reasons for unavailable assessments.
The number analyzed for the primary endpoint is not reported in the registry record. Enrollment of 579 should therefore not be assumed to be the primary analysis denominator. Nor should the safety count of 542 at risk be substituted for the endpoint population, because the record does not identify it as the denominator for the primary outcome. The record also does not describe whether participants were included in each time-point analysis on the same basis or how incomplete follow-up was handled.
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 |
|---|---|---|---|
| Sodium Risedronate 75 mg | 4 | 542 | 0.7% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sodium Risedronate 75 mg | 0 of 542 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sodium Risedronate 75 mg | 7 of 542 |
Most frequent serious adverse event terms
| Event term | Organ system | Sodium Risedronate 75 mg |
|---|---|---|
| Toothache | Gastrointestinal disorders | 1 of 542 |
| Osteonecrosis | Musculoskeletal and connective tissue disorders | 1 of 542 |
| Femur fracture | Injury, poisoning and procedural complications | 1 of 542 |
| Hospitalisation | Surgical and medical procedures | 1 of 542 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sodium Risedronate 75 mg |
|---|---|---|
| Nausea | Gastrointestinal disorders | 7 of 542 |
Serious events with the highest arm-level rate: toothache (0.2%), osteonecrosis (0.2%), femur fracture (0.2%), hospitalisation (0.2%).
The safety figures list 542 participants at risk in the Sodium Risedronate 75 mg group. The record lists 4 serious adverse event reports and 7 reports in the other adverse-event category, with 0 deaths. These are descriptive counts from the registry record; the method used to define or collect each category is not reported in the registry record.
The listed serious-event terms are Toothache, Osteonecrosis, Femur fracture, and Hospitalisation, each reported as 0.2%. These terms should be read as event descriptions, not as evidence that the drug caused the events. The registry record does not provide a comparator group or a causal analysis. It also does not state whether the terms represent distinct participants, whether participants could have more than one event, or the event timing and duration.
In general, counts and percentages in a safety summary describe events recorded in the observed group, while a comparison is needed to assess whether event frequency differs between groups. The safety denominator of 542 is not the same as the listed enrollment of 579, and the registry does not explain the difference. The reported 0 deaths means no deaths are listed in this safety summary; it does not establish that risk was absent or that no deaths occurred outside the recorded group or period.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed special drug use surveillance was registered for sodium risedronate 75 mg in people with osteoporosis, with a primary endpoint defined around new or worsening vertebral body fractures over follow-up up to Month 36. It also specifies the intended assessment times and defines an assessment population requiring survey completion and evaluable fracture data.
What it does not establish from the posted results is the observed cumulative fracture percentage. The primary estimate, its 95% confidence interval, and the number analyzed are not reported in the registry record. Without those values, the frequency of the primary outcome and the precision of its estimate cannot be described. Numerical findings for the listed secondary outcomes are also not reported in the registry record.
Even if a primary percentage were available, a single-group surveillance would describe the observed group rather than establish a treatment effect relative to a comparator. The record lists no comparator, states no allocation method, and is not a randomized comparison. Consequently, the design does not provide a like-for-like control comparison that could separate outcomes during treatment from outcomes that might otherwise occur.
The safety summary records adverse-event counts and serious-event terms, but these data do not establish causation. The registry does not provide a comparative safety analysis, event-level details, or an explanation of the difference between enrollment and the safety group at risk. The listed death count should be understood as a record entry, not as proof of no risk.
In general, registry information is most informative when outcome definitions, analysis populations, missing-data methods, and numerical results are all available. Here, the record describes the intended surveillance and some safety observations, but the absent primary and secondary outcome results limit conclusions about what was observed during follow-up.
13. Why This Trial Matters Statistically
This surveillance illustrates why a clearly named endpoint is not enough to interpret a clinical result. The primary question is concrete: the cumulative percentage of participants with new or worsening vertebral body fractures from baseline up to Month 36. Yet the numerical estimate, confidence interval, and analyzed denominator are not reported in the registry record. Without those elements, neither the outcome frequency nor its precision can be evaluated.
The record also highlights the importance of matching the denominator to the question. Enrollment is 579, the safety group at risk is 542, and the primary assessment population is defined by completion and evaluable fracture data. These counts refer to distinct aspects of the record; the primary analysis count is not reported. Treating enrollment as the endpoint denominator would therefore go beyond the documented information.
Design matters as much as endpoint choice. The surveillance concerns treatment in routine medical care and lists no comparator. A descriptive event percentage can inform what was recorded in the observed group, but it is not a controlled treatment contrast. This distinction remains important even when a study is completed and follows participants over a stated period.
Finally, the record names a broad set of secondary fracture, bone density, and marker outcomes, while reporting no analyses. That gap makes it impossible to assess the full pattern of outcomes or how multiple questions were handled. For biostatisticians and clinical researchers, the example underscores the value of transparent reporting of analysis populations, missing data, interval estimates, and prespecified statistical methods alongside outcome definitions.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The main limitation for interpreting this surveillance is that numerical results for the primary endpoint are not reported in the registry record. The 95% confidence interval is named, but neither its limits nor the underlying percentage is posted. The number analyzed at each assessment time is also absent, preventing evaluation of the denominator and precision.
The record lists no comparator and does not state an allocation method. It is not a randomized comparison, so the observed group cannot be contrasted with a like-for-like control group using the information available. The treatment was described as part of routine medical care, but details about adherence, treatment changes, concomitant care, and monitoring are not reported in the registry record.
The primary assessment population requires survey completion and evaluable vertebral fracture information at baseline and post-baseline times. The number of participants who met that definition, the amount and pattern of missing data, and the handling of incomplete follow-up are not reported. This limits understanding of how representative the analyzed population might be of all enrolled participants.
The fracture classification procedures and the statistical approach for calculating the cumulative percentages and confidence intervals are not reported in the registry record. Nor are multiplicity procedures, interim analyses, or a statistical analysis plan described. The record lists 15 outcome measures but reports no analyses, leaving the numerical findings across the outcome set unavailable.
For safety, the record lists 542 at risk, but it does not explain how this group relates to enrollment of 579. The event summaries do not include detailed timing, duration, participant-level overlap, or comparative attribution. These limitations mean the safety entries are best read as descriptive registry information rather than evidence of causal relationships.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: 36-month Special Drug Use Surveillance on Frequency of Bone Fractures With Sodium Risedronate 75 mg Tablets — NCT02106442.
- Registry record last updated 2019-07-30; status last verified 2019-07.
- Results first posted 2019-07-17.
- 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 completed special drug use surveillance concerns sodium risedronate 75 mg in people with osteoporosis receiving routine medical care. Enrollment is listed as 579, and the primary endpoint is the cumulative percentage with new or worsening vertebral body fractures from baseline up to Month 36. Assessments are described at baseline and Months 6, 12, 18, 24, 30, and 36.
The primary assessment population requires survey completion and evaluable baseline and post-baseline fracture data. Its analyzed size, the primary estimate, and the 95% confidence interval are not reported in the registry record. Secondary fracture, bone density, and bone marker outcomes are listed, but their numerical findings are also not reported. The record lists no comparator and is not a randomized comparison.
The safety summary lists 542 at risk, 4 serious adverse event reports, 7 reports in the other adverse-event category, and 0 deaths. Four serious-event terms are listed at 0.2% each. These data are descriptive and do not establish causation.