FOSAMAX PLUS and FOSAMAX PLUS D Re-examination Study (0217A-267): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for FOSAMAX PLUS and FOSAMAX PLUS D Re-examination Study (0217A-267) (NCT01065779), a registered phase not stated study. The primary outcome is Number of Participants With Serious Adverse Events.

2. Clinical Question

3. Trial Design

This completed study is registered as a re-examination study for general drug use. Its stated purpose was to prepare application materials for re-examination under the Pharmaceutical Affairs Laws and its Enforcement Regulation, and to reconfirm the clinical usefulness of FOSAMAX PLUS and FOSAMAX PLUS D by collecting safety information under the Re-examination Regulation for New Drugs. The registry describes the setting as usual practice rather than a randomized treatment comparison.

The record lists an enrollment of 880 and describes one combined treatment group: participants with osteoporosis treated with FOSAMAX PLUS (70 mg/2800 IU) or FOSAMAX PLUS D (70 mg/5600 IU). It does not report separate enrollment or outcome totals for each product. Allocation is not stated, and there is no like-for-like control comparison described. Consequently, the study record supports a descriptive account of observed events in treated participants, not a direct estimate of a treatment contrast.

The study started in 2006-03, had primary completion in 2010-07, and is marked COMPLETED. The primary safety evaluation population was defined as participants who took at least one dose of study medication and completed > 1 follow-up visit. That population comprised 798 participants. The registry does not explain the difference between the listed enrollment and the safety evaluation population, so reasons for participants not appearing in that evaluation cannot be inferred from these figures alone.

The registry lists 8 outcome measures and 0 analyses. The primary outcome is the number of participants with serious adverse events. Further details about the protocol, planned statistical analyses, sample-size justification, or any interim analyses are not reported in the registry record. A completed status indicates the study is recorded as completed; it does not by itself establish that every planned result or analysis is available in the 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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety evaluation was performed in participants who took at least one dose of study medication and completed \> 1 follow up visit.

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Serious Adverse Events, measured over Up to ~ 16 weeks and 14 days after treatment discontinuation.

The primary endpoint is the number of participants who experienced at least one serious adverse event. The registry defines serious events by consequences including death or a life-threatening event, prolonged inpatient hospitalization, persistent or significant disability or incapacity, a congenital anomaly or birth defect, or another important medical event judged significant by the investigator. The unit is participants, so the result is a count of people meeting the serious-event definition rather than a count of every event episode.

The outcome is used to describe serious safety events in participants exposed to the study medication. Such an endpoint focuses on events considered consequential under the registry definition. It does not capture every possible adverse event, and the primary outcome should not be read as a complete summary of all safety information. The registry says routine visits for adverse-event assessment were not required. Events were collected through participant self-reporting and assessed by investigators, which describes the collection and assessment approach but does not establish that every event was detected.

The recorded result is zero participants with serious adverse events among 798 participants in the safety evaluation population. The stated timeframe extends up to approximately 16 weeks and 14 days after treatment discontinuation. The record does not report a comparison group or separate serious-event counts for the two products.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a binary participant-level event outcome: each person either met the serious-adverse-event definition during the specified period or did not. The posted result is expressed as a count of participants with an event, rather than as a model-based estimate. For a binary outcome, an analysis might report the event count alongside the number evaluated, and could also estimate an event proportion with an interval describing uncertainty. The registry reports the count and evaluation population size, but it does not report a confidence interval or a formal analysis for this endpoint.

What does a zero event count convey?

A zero observed count is a factual description of the evaluated group. It is not proof that the event is impossible or that its underlying frequency is exactly zero. In general, estimates from finite groups have uncertainty, and a confidence interval can help show the range of values compatible with the observed data under a specified method. No interval is reported in the registry record, so no numerical precision range can be attributed to this outcome from the record.

The count is also tied to the endpoint definition. Serious events included specified consequences such as death, life-threatening events, prolonged hospitalization, significant disability or incapacity, congenital anomaly or birth defect, and other important medical events judged significant by the investigator. The primary count is therefore not a count of all adverse events, nor does it describe the severity or frequency of non-serious events. The record states that adverse events were self-reported by participants and assessed by investigators, and that there was no required routine visit scheduled for adverse-event assessment.

Why is the study not a treatment comparison?

A treatment comparison generally needs groups whose outcomes can be contrasted, along with a design and analysis that make the contrast interpretable. Here, the registry describes one combined group of participants receiving FOSAMAX PLUS or FOSAMAX PLUS D. Allocation is not stated, and the record identifies no like-for-like control comparison. Separate outcome counts for the two formulations are also absent. The result therefore describes events in the combined evaluated group; it does not estimate a difference between the products or against a control.

In general, randomization can help balance prognostic factors between treatment groups, while non-randomized treatment allocation can leave differences between groups that affect outcome comparisons. The registry does not state how treatment was allocated. It would therefore be inappropriate to assume a randomization procedure or to claim that any comparison has the protections associated with random allocation.

What do the planning illustrations mean?

Sample-size planning calculations are not observed outcomes. The stated planning approach uses a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect set as a stated fraction of the observed effect. These are planning assumptions, not evidence that the study was designed with those assumptions. The registry does not report the study's own sample-size justification, and the reported study is not a two-arm randomized comparison. Any planning illustration should therefore be understood as hypothetical rather than as the trial's original design or as observed power.

In general, power is a design-stage probability of detecting an effect under specified assumptions. It is not a measure of how likely a result is to be true after the study is complete. A sample-size illustration based on an observed effect also depends on the assumed effect size and analysis model; it cannot repair the absence of a control comparison or establish a causal effect. No new sample-size values or power estimates are stated in this interpretation.

What can be said about analysis choices?

The record lists 8 outcome measures and 0 analyses. It does not report the statistical plan, model specifications, confidence-interval method, interim analyses, adjustment for multiple outcomes, or rules for handling missing outcome data. Thus, there is no basis in the registry record to describe a particular inferential method as the study's planned or completed analysis. General statistical principles can help explain why such choices matter, but they should not be mistaken for methods documented for this study.

For example, over-dispersion is a concern in some count-data models when variability exceeds what the chosen model expects. It is not an issue that can be assessed from this primary participant count alone, and the registry does not report a count-data model. Similarly, covariate adjustment may be useful in specified analyses, but no adjusted estimate is reported. The result available for the primary endpoint is the descriptive count of zero among 798 evaluated participants.

Finally, the enrollment figure and the safety evaluation population describe different counts. The registry does not explain the participant-level flow between them. No derivation of exclusions, losses to follow-up, or outcome status for people outside the safety population should be inferred from the counts alone.

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("FOSAMAX PLUS/ FOSAMAX PLUS D")
n      <- c(798)
events <- c(0)
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  FOSAMAX PLUS/ FOSAMAX PLUS D  798  0  0.0  0.0  0.5  0.0  0.5  0.0  0.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 8 outcome measures and 0 analyses. The primary outcome is the number of participants with serious adverse events. Definitions and results for the other listed measures are not reported in the registry record. The record also does not report whether outcomes were ranked in a prespecified hierarchy or whether any adjustment for multiple testing was planned. When many outcomes are examined, the chance of at least one apparently unusual result can increase; in general, multiplicity methods address that issue. No specific method can be attributed to this study.

The primary safety population included participants who took at least one dose and completed > 1 follow-up visit. Its reported size is 798, while enrollment is listed as 880. The registry does not provide a participant-flow explanation for the difference, the number of participants excluded for each reason, or their outcome status. It does not report an intention-to-treat population or another analysis population definition beyond the safety evaluation description.

Missing-data rules, imputation methods, sensitivity analyses, and approaches to incomplete adverse-event reporting are not reported in the registry record. The stated assessment process relied on participant self-reporting and investigator assessment, with no required routine visit scheduled for adverse-event assessment. These details describe data collection but do not quantify missingness or show how it was handled. Consequently, the reported zero event count applies to the defined safety evaluation population and should not be generalized to participants whose inclusion or follow-up status is not described.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

The serious-adverse-event result is 0 participants among 798 in the safety evaluation population. The population comprised participants who took at least one dose and completed > 1 follow-up visit. The stated observation period was up to approximately 16 weeks and 14 days after treatment discontinuation. The result concerns participants with at least one event meeting the registry's seriousness criteria, not the total number of all adverse events.

The registry says routine visits for adverse-event assessment were not required. Events were collected through participant self-reporting and assessed by investigators. The record does not report a confidence interval, the number of non-serious adverse events, separate counts for FOSAMAX PLUS and FOSAMAX PLUS D, or a control-group result. Zero recorded serious events is therefore a description of what was observed in the defined group, not evidence that the true risk is zero or that one formulation is safer than another.

Interpret the count within its population, timeframe, event definition, and collection approach. The registry does not report outcomes for participants outside the safety evaluation population or explain the enrollment-to-evaluation flow. Those omissions limit conclusions about the broader enrolled group.

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

The main statistical meaning is narrow and concrete: among 798 participants included in the defined safety evaluation population, the registry reports 0 participants with serious adverse events during the stated observation period. The outcome uses the registry's seriousness criteria and combines people treated with FOSAMAX PLUS and FOSAMAX PLUS D. It is a description of the observed group, not a comparative estimate.

The finding does not show that serious adverse events cannot occur. In general, a finite observation group can have no recorded events even when an underlying event probability is greater than zero. Precision depends on the amount and quality of follow-up as well as the number evaluated. No confidence interval is reported in the registry record, so the result has no reported numerical uncertainty interval to quote.

The finding also does not establish whether either formulation has a different safety profile from the other. The registry gives no separate product-specific outcome counts and no control group. Allocation is not stated. Without a suitable comparison and its supporting design details, the record cannot estimate a treatment difference or attribute the observed count to a treatment effect.

The result should not be taken as a complete account of adverse events. It concerns serious adverse events as defined in the record; other adverse-event categories are not part of this primary count. The registry describes self-reporting and investigator assessment, with no required routine visit for adverse-event assessment. It does not report the extent of missing information or how incomplete reporting was addressed.

Nor does the record establish the rationale for enrollment, the statistical plan, or the handling of all 8 listed outcome measures. The listed enrollment is 880, whereas the safety evaluation population is 798; reasons for that difference are not reported. The appropriate conclusion is limited to the posted descriptive count and its specified population and timeframe, without inferring unreported outcomes or causal effects.

14. Why This Trial Matters Statistically

This study illustrates why the statistical meaning of a safety count depends on more than the number itself. The registry reports zero participants with serious adverse events, but that count is interpretable only alongside its event definition, evaluated population, follow-up period, and collection approach. Those details define what the result covers and what it leaves out.

The record also illustrates the distinction between describing an exposed group and comparing treatments. FOSAMAX PLUS and FOSAMAX PLUS D are reported together, with no separate outcome counts, control group, or stated allocation method. A descriptive result can document what was recorded in the evaluated participants, but it cannot by itself quantify a treatment difference or establish causality. Clear distinction between those purposes helps prevent an event count from being overread.

Population definitions matter as well. The safety evaluation was restricted to participants who took at least one dose and completed > 1 follow-up visit. The enrollment total is 880 and the evaluated population is 798, but the registry does not explain the participant flow between those counts. Such omissions limit assessment of how broadly the result applies and whether participants not included in the safety evaluation had different follow-up or outcomes.

Finally, the record lists multiple outcome measures but no analyses. It does not report a statistical plan, handling of missing data, multiplicity procedures, or an interval estimate for the primary count. These are not minor details when readers want to judge uncertainty and completeness. The example underscores a general principle: a simple, clearly stated event count can be useful, while the strength and scope of conclusions remain bounded by design, population, follow-up, and reporting.

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 study is described as a usual-practice re-examination survey, not a randomized comparison. Allocation is not stated, and no like-for-like control group is described. The registry combines participants receiving FOSAMAX PLUS and FOSAMAX PLUS D in one group and does not report their outcomes separately. The primary result therefore cannot distinguish the safety findings for the two formulations or estimate a treatment contrast.

The primary evaluation population included only participants who took at least one dose and completed > 1 follow-up visit. Although enrollment is listed as 880, the safety population is 798. Reasons for this difference, participant disposition, and outcome status outside the safety population are not reported in the registry record. This makes it difficult to assess the completeness and representativeness of the evaluated group.

Adverse events were collected through participant self-reporting and assessed by investigators, and no routine visit for AE assessment was required. The record does not quantify how complete event ascertainment was, describe any additional surveillance, or report how missing information was handled. The outcome is limited to serious adverse events under the stated definition; counts for non-serious events and other safety categories are not reported in the registry record for this analysis.

The registry lists 8 outcome measures but 0 analyses. The statistical analysis plan, sample-size justification, interim analyses, confidence intervals, multiplicity approach, and missing-data methods are not reported. The primary result is thus available as a descriptive count without reported inferential estimates or details for assessing statistical precision. The specified timeframe also bounds the finding: it extends up to approximately 16 weeks and 14 days after treatment discontinuation, not beyond the period described.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: FOSAMAX PLUS and FOSAMAX PLUS D Re-examination Study (0217A-267) — NCT01065779.
• Registry record last updated 2022-02-03; status last verified 2022-02.
• Results first posted 2011-09-13.
• 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

NCT01065779 is a completed usual-practice re-examination study of FOSAMAX PLUS and FOSAMAX PLUS D in participants with osteoporosis. The record lists enrollment of 880, a start in 2006-03, and primary completion in 2010-07. Its stated purpose was to collect safety information for re-examination materials and reconfirm clinical usefulness under the relevant re-examination regulation.

The primary outcome was the number of participants with serious adverse events up to approximately 16 weeks and 14 days after treatment discontinuation. The safety evaluation population was defined as participants who took at least one dose and completed > 1 follow-up visit. The registry reports 0 participants with serious adverse events among 798 in that population.

The record lists one combined treatment group, 8 outcome measures, and 0 analyses. It does not report separate results for the two formulations, a control comparison, or the statistical plan and missing-data methods. The result is therefore a descriptive safety count for the defined population and period.