Sodium Risedronate Tablets - Special Drug Use Surveillance in Patients With Osseous Paget's Disease (All-case Surveillance) -48-week Surveillance -: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sodium Risedronate Tablets - Special Drug Use Surveillance in Patients With Osseous Paget's Disease (All-case Surveillance) -48-week Surveillance - (NCT02106455), a registered phase not stated study. The primary outcome is Percentage of Participants Who Had One or More Adverse Drug Reactions.

2. Clinical Question

The study concerns patients with osseous Paget's disease and evaluates sodium risedronate in daily medical practice. Its stated purpose is to assess safety and efficacy over 48 weeks from baseline. The clinical question is therefore how safety and disease-related measures were assessed during surveillance of patients receiving the drug, rather than whether the drug outperformed a randomized control group.

Secondary outcomes include changes in serum alkaline phosphatase and urinary bone-turnover markers, pain assessments, and imaging assessments of bone abnormalities. The record names these outcomes but does not provide their results in the registry record for this analysis. It therefore supports a description of the surveillance question and its outcome framework, but not a numerical assessment of the primary endpoint or the secondary measures.

3. Trial Design

This is an all-case special drug use surveillance study of sodium risedronate in patients with osseous Paget's disease. It is marked completed and lists an enrollment of 315. The record identifies Takeda as the sponsor and gives a study start of 2008-08-01 and primary completion of 2017-10-24. These dates describe the study record; they do not by themselves establish the length of treatment or follow-up for an individual participant.

The study's stated purpose is to evaluate safety and efficacy in daily medical practice over 48 weeks from baseline. The intervention is sodium risedronate, with the arm description specifying a 17.5 mg oral dose once daily after waking, taken with a sufficient volume of water, for 8 consecutive weeks. Because the purpose describes 48-week surveillance while the arm description specifies 8 weeks of administration, the registry text distinguishes the surveillance timeframe from the stated dosing period. Further detail about treatment after that period is not reported in the registry record.

No randomized control comparison is described, and allocation is not stated. The study should therefore be read as surveillance of treated patients, not as a randomized test against a comparable untreated or active-control group. The primary endpoint concerns adverse drug reactions up to 48 weeks. Secondary outcomes cover biochemical measures, pain, and imaging findings at the final assessment point.

The safety analysis set is defined as all participants who completed the study. Although enrollment is listed as 315, the safety figures use 307 participants at risk for each of the listed categories. The registry record does not explain the difference between these figures or provide further analysis-population details. It reports 11 outcome measures and 0 analyses in the registry entries, so detailed statistical procedures and numerical results for the stated efficacy outcomes are not available in this 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: Participants with a historical diagnosis of osseous Paget's disease were enrolled. Participants received interventions as part of routine medical care.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Analysis Set; The safety analysis set was defined as all participants who completed the study.

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 study.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Had One or More Adverse Drug Reactions, measured over Up to 48 weeks.

The primary endpoint is the percentage of participants who had one or more adverse drug reactions up to 48 weeks. The record defines an adverse drug reaction as an adverse event related to the administered drug. The endpoint is intended to describe the proportion of the specified safety population experiencing at least one such reaction during the stated timeframe.

Counting participants with one or more reactions focuses on whether a participant experienced an event, rather than how many events each participant experienced. It is a participant-level safety summary. The endpoint's meaning depends on how adverse events were identified, judged to be related to the drug, and collected over follow-up. Those operational details are not reported in the registry record beyond the definition of an adverse drug reaction and the timeframe.

The safety analysis set is defined as participants who completed the study. That definition matters because the endpoint is described as a percentage, but the record does not give a primary-endpoint numerator, denominator, or percentage in the registry record. The safety figures reported separately do not establish the primary endpoint result: they are presented as serious and other adverse-event counts, and the record does not state that either count is the number of participants with one or more adverse drug reactions.

A percentage of participants with a reaction can help characterize observed safety in the surveillance population. It does not, by itself, show that the drug caused every recorded event, establish comparative risk, or describe event severity and duration. The endpoint result and the methods used to determine drug relatedness are not reported in the registry record, limiting the conclusions that can be drawn from this measure.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The available record describes the study and its endpoints but reports 0 analyses. It does not specify an inferential statistical plan, adjustment strategy, or model for the primary endpoint. The methods discussion below distinguishes what is described from general statistical interpretation; it does not imply that a particular unreported method was used.

What does a participant-level percentage represent?

In general, a participant-level percentage for an event counts each participant no more than once, even if that participant experiences multiple events. This differs from an event count, which can include repeated events in the same participant. The primary endpoint is defined as the percentage with one or more adverse drug reactions. The registry does not report its numerator, denominator, or result, so that percentage cannot be reconstructed from the listed safety figures.

For such a percentage, the analysis population and follow-up window are essential. Here, the primary timeframe is up to 48 weeks, and the safety analysis set is defined as participants who completed the study. The record does not explain how participants with incomplete follow-up were handled, whether all members of that set were observed for the same duration, or how missing adverse-event information was treated.

How should uncertainty be understood?

In general, a confidence interval describes the statistical uncertainty around an estimate under the assumptions of the method used. A narrow interval indicates greater precision than a wide interval, but neither interval alone resolves bias, confounding, or limitations in event ascertainment. No confidence interval for the primary endpoint or the listed safety figures is reported in the registry record. No p-value or hypothesis test for these outcomes is reported either.

Because the surveillance study is not a randomized comparison and allocation is not stated, an inferential comparison between treatment groups is not described. In general, random allocation helps balance measured and unmeasured characteristics between groups, while an uncontrolled or non-randomized design can leave differences in patient characteristics and care as alternative explanations for observed outcomes. That is a design consideration, not a claim that a particular bias occurred in this study.

What do the planning illustrations mean?

The planning illustrations are described as calculations based on an observed effect, not as the trial's own design justification. They assume a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a stated fraction of the observed effect. For time-to-event settings, the stated method gives the total number of events using Schoenfeld; for other settings, it gives participants per arm.

In general, such calculations show how a hypothetical future study's size might vary under chosen assumptions. They are not observed outcomes, do not establish the study's actual power, and cannot be interpreted as evidence that the study was designed around those assumptions. The sample-size justification for this surveillance study is not reported in the registry record. The registry entries available do not provide specific planning-illustration values, so no numerical planning result can be interpreted.

What can the listed adverse-event figures establish?

The record lists affected-participant counts separately for serious and other adverse events, with 307 participants at risk in each category. In general, counts describe how many participants were recorded in a category; they do not reveal event timing, recurrence, duration, or a causal relationship to treatment. Seriousness and drug relatedness are distinct classifications: an event can be serious without being judged related to treatment, and an event judged related need not be serious. The registry's primary endpoint concerns drug-related events, while the separate safety counts are not identified as that endpoint's result.

The listed serious terms are accompanied by percentages, but the record does not state how those percentages were calculated or provide uncertainty estimates for them. No new percentage should be derived from the counts without knowing the relevant definitions and analysis population. In general, when event frequencies are small, estimates can be imprecise; the record does not provide enough information to quantify that uncertainty for these terms.

What is missing from the statistical description?

The registry record does not report the statistical analysis plan, interim analyses, missing-data procedures, multiplicity adjustments, or model-based results. It also does not report confidence intervals or hypothesis tests. These omissions mean that the statistical significance, precision, and robustness of the stated efficacy outcomes cannot be assessed from the available record. The study's 11 outcome measures identify a range of questions, but without results and analysis details they do not establish findings for those questions.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Sodium Risedronate 17.5 mg")
n      <- c(307)
events <- c(46)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Sodium Risedronate 17.5 mg  307  46  15.0  11.2  19.5  11.4  19.4  11.4  19.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary adverse drug reaction endpoint and secondary measures covering biochemical markers, pain, and imaging. Considering multiple outcomes can raise a multiplicity issue: in general, testing several hypotheses can increase the chance that at least one result appears statistically notable by chance. The appropriate response depends on the study objectives and prespecified analysis plan. The registry record does not report whether outcomes were tested statistically or whether any multiplicity adjustment was planned or used.

The record reports 0 analyses in the registry entries. It does not provide p-values, confidence intervals, or inferential results for the primary or secondary outcomes. Accordingly, there is no basis in this record to describe an adjustment method, distinguish confirmatory from exploratory analyses, or assess the effect of multiplicity on reported findings.

Missing-data handling is also not reported in the registry record. The safety analysis set is defined as all participants who completed the study, but there is no account of participants who did not complete it, the amount or pattern of missing outcome data, or any imputation or sensitivity analysis. A completion-based safety population can differ from the enrolled population; the record does not explain the reasons for any difference between the enrollment figure and the safety counts.

The record does not provide analysis populations for the secondary outcomes or explain whether their denominators differed from the safety analysis set. It also does not report a protocol-level statistical analysis plan, interim analyses, or the sample-size justification. These gaps limit assessment of selective outcome reporting, missing-data bias, and the intended interpretation of any statistical tests. They should be treated as unreported information, not as evidence that a particular procedure was or was not performed.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hypocalcaemia (0.7%), pneumonia (0.3%), cerebral infarction (0.3%), depressed level of consciousness (0.3%), dysarthria (0.3%).

The registry lists 307 participants at risk for serious events and 15 affected participants in that category. For other adverse events, it lists 307 at risk and 14 affected. It also reports 0 deaths. These are counts of participants in the listed safety categories, not a randomized comparison. The record does not state that these counts are the primary endpoint of participants with one or more adverse drug reactions.

The serious terms reported are hypocalcaemia at 0.7%, and pneumonia, cerebral infarction, depressed level of consciousness, dysarthria, and pericardial effusion, each at 0.3%. These are the percentages as recorded. The registry record does not provide the underlying counts for each term, explain whether a participant could contribute to more than one term, or state the method used to calculate the percentages.

Seriousness, occurrence, and drug relatedness are not interchangeable concepts. The primary endpoint is specifically about adverse events related to the administered drug, whereas the listed serious-event figures do not establish that those events were judged related. Nor do the counts describe timing, duration, recurrence, or clinical course. Without a control group, these observations cannot establish whether the events occurred more or less often because of treatment.

The safety analysis set is defined as participants who completed the study. Further details about follow-up, incomplete records, and event ascertainment are not reported in the registry record. The figures therefore provide a limited descriptive account of recorded safety categories, not a complete characterization of safety risk or a causal assessment.

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

The record establishes that a completed all-case surveillance study evaluated sodium risedronate in patients with osseous Paget's disease. It describes a primary safety endpoint, a 48-week surveillance timeframe, an 8-week dosing description, and secondary outcomes involving biochemical markers, pain, and imaging. It also gives selected safety counts and serious-event terms. These registry entries describe the study's scope and the information recorded, but they do not supply a numerical result for the primary endpoint.

The primary outcome result is not reported in the registry record. No results for the listed secondary outcomes are available in the registry record used for this analysis. The study's stated purpose to evaluate safety and efficacy should not be mistaken for evidence of a particular safety or efficacy finding. The safety figures can be read descriptively, but they do not provide a comparison with another treatment group or establish that an event was caused by sodium risedronate.

In general, a non-randomized surveillance study can describe events occurring in routine practice, while a like-for-like comparison is needed to estimate relative outcomes between groups with stronger control of alternative explanations. Here, allocation is not stated and no randomized comparison is described. The figures therefore cannot establish a comparative treatment effect.

The information also does not quantify uncertainty around the primary or secondary outcomes. Confidence intervals, hypothesis tests, and analysis details are not reported. Missing-data methods and the sample-size justification are not reported either. Consequently, the precision and robustness of the outcomes cannot be assessed from the available record.

The most defensible interpretation is narrow: the registry records a surveillance study with stated outcome objectives and selected safety information, while leaving the primary endpoint result and efficacy results unavailable. It does not support a conclusion about whether treatment improves disease outcomes, changes risk relative to another option, or produces a particular overall safety profile. Those conclusions would require reported outcome data and, for comparative claims, a suitable comparison design.

14. Why This Trial Matters Statistically

This study illustrates an important distinction in clinical statistics: a clearly stated objective does not guarantee that the result needed to answer it is available in a registry record. The primary endpoint is defined as the percentage of participants with one or more adverse drug reactions up to 48 weeks, yet its result is not reported in the available information. Without the estimate and its denominator, readers cannot assess the endpoint's observed frequency or precision.

The design also matters. All-case surveillance can describe safety observations in patients receiving a treatment in daily medical practice. It does not, on its own, create a randomized comparison. Since allocation is not stated and there is no like-for-like control group, the listed safety information cannot isolate a treatment effect from other possible influences. That distinction is central when interpreting event counts as descriptive observations rather than causal evidence.

The record also shows why population definitions need careful reading. Enrollment is listed as 315, while the safety counts use 307 participants at risk. The safety analysis set is defined by study completion, but the record does not explain the difference or provide details about missing follow-up. Denominators shape the interpretation of percentages and should be reported alongside clear population and follow-up definitions.

Finally, multiple outcome domains are named, but the statistical analyses are not reported. Without results, uncertainty estimates, missing-data procedures, and multiplicity information, readers cannot assess how precisely the study answers its stated questions. The example underscores that registry design details, endpoint definitions, analysis populations, and posted results each contribute different pieces of evidence; none can substitute for the others.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record leaves several study-specific details unavailable. It does not state allocation, and no randomized comparison is described. As a result, the record does not support a like-for-like control comparison or a causal estimate of treatment effects.

The study purpose describes surveillance over 48 weeks from baseline, while the arm description specifies daily sodium risedronate administration for 8 consecutive weeks. The record does not further explain treatment or observation after the specified dosing period. The primary endpoint timeframe is stated as up to 48 weeks, but the details of follow-up and event collection are not reported.

The primary endpoint result is not reported, and the listed secondary outcomes have no results in the registry entries. Although the safety figures include participants at risk, affected participants, deaths, and selected serious terms, the record does not explain the difference between enrollment of 315 and the 307 participants at risk. It also does not provide the underlying counts for each listed serious term or explain how the percentages were calculated.

The safety analysis set is defined as participants who completed the study. Reasons for non-completion, missing-data handling, and the analysis populations for other outcomes are not reported. The registry record also does not provide an analysis plan, interim analysis details, multiplicity procedures, confidence intervals, hypothesis tests, or the sample-size justification. The planning illustrations described separately are not the trial's original design justification and should not be interpreted as observed power.

These limitations constrain interpretation of both safety and efficacy. They do not show that an unreported procedure was absent; they mean that the available record does not document it. The design and reporting details are insufficient to estimate comparative effects or assess the precision of the primary endpoint.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Sodium Risedronate Tablets - Special Drug Use Surveillance in Patients With Osseous Paget's Disease (All-case Surveillance) -48-week Surveillance - — NCT02106455.
• Registry record last updated 2019-06-03; status last verified 2019-02.
• Results first posted 2019-06-03.
• 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.

19. Record Summary

This completed all-case surveillance study concerns sodium risedronate in patients with osseous Paget's disease. Enrollment is listed as 315. The study purpose describes safety and efficacy evaluation over 48 weeks from baseline; the intervention description specifies 17.5 mg orally once daily for 8 consecutive weeks. The primary endpoint is the percentage of participants with one or more adverse drug reactions up to 48 weeks, with the safety analysis set defined as participants who completed the study.

The record lists 307 participants at risk for serious events, with 15 affected, and 307 at risk for other events, with 14 affected. It reports 0 deaths and lists selected serious-event terms with percentages. The primary endpoint result and secondary outcome results are not reported in the available information. Allocation is not stated, and the study is not a randomized comparison. The statistical analysis plan, missing-data procedures, multiplicity methods, and sample-size justification are not reported in the registry record.