BONCURE Study: A Study of Monthly Bonviva (Ibandronate) in Women With Post-Menopausal Osteoporosis on Bisphosphonate Therapy.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BONCURE Study: A Study of Monthly Bonviva (Ibandronate) in Women With Post-Menopausal Osteoporosis on Bisphosphonate Therapy. (NCT00545779), a na phase 3 study. The primary outcome is Percentage of Participants Current Daily or Weekly Bisphosphonate Users in Part A Who Answer 'Yes' to Any of the Questions in the Candidate Identification Questionnaire (CIQ).

2. Clinical Question

BONCURE addressed treatment preference and reported experiences, rather than a randomized comparison of clinical outcomes. The Candidate Identification Questionnaire asked whether participants preferred a monthly schedule, had experienced stomach upset within 48 hours of taking their osteoporosis medication more than once per month, or had missed three or more doses of their current medication over the past 3 months. A “yes” to any one of these questions counted toward the primary outcome.

The study then used the questionnaire to identify participants for whom monthly ibandronate might be a more satisfactory option. Participants eligible to continue entered Part B and switched to monthly treatment. Other questions considered satisfaction, compliance, reminders, gastrointestinal symptoms, and questionnaire scores. The registry record does not report numerical results for these outcomes, so it does not establish how often participants selected any particular response or how their satisfaction changed.

3. Trial Design

BONCURE is recorded as a Phase 3, open, prospective, multicenter, two-part, single-group study. The registry lists 677 enrolled participants and Hoffmann-La Roche as sponsor. The study began in 2006-12, had primary completion in 2008-10, and is recorded as completed.

In Part A, participants completed the Candidate Identification Questionnaire while using daily or weekly bisphosphonate therapy. The primary outcome concerned whether they answered “yes” to any of its three questions. Part B involved monthly oral ibandronate for up to 6 months. The arm description specifies a 150 mg tablet taken once monthly. The brief summary describes an anticipated treatment period of 3-12 months, while the arm description specifies treatment up to 6 months; the registry record does not explain this difference.

There was no masking, and allocation is recorded as not applicable. The design is listed as single group, with no concurrent control arm. Thus, the prior daily or weekly regimen provides background for the preference questions, not a randomized comparison. The study summary describes a target sample size of 500+ individuals; actual enrollment was 677.

The primary outcome was measured at Visit 0, described as less than or equal to Day -30. The registry identifies the primary population as all enrolled participants who completed Part A. It does not report a protocol-level sample-size justification, recruitment details, or statistical analysis plan. The registry also does not provide numerical outcome results or analysis entries.

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: All enrolled participants who completed the part A of 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: Analysis population included all enrolled participants in Part A who provided the baseline information.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Current Daily or Weekly Bisphosphonate Users in Part A Who Answer 'Yes' to Any of the Questions in the Candidate Identification Questionnaire (CIQ), measured over Visit 0 (less than or equal to [<=] Day -30).

The primary endpoint is the percentage of current daily or weekly bisphosphonate users in Part A who answered “yes” to any question in the Candidate Identification Questionnaire. The questionnaire asked about preference for monthly rather than current dosing, stomach upset within 48 hours of medication use more than once per month, and missing three or more doses over the past 3 months. The primary population is described as all enrolled participants who completed Part A.

This endpoint combines three possible reasons for considering a monthly regimen into a single binary classification: a participant either answered “yes” to at least one item or did not. In general, a percentage endpoint can describe how common a specified response was within a defined population. Here, the endpoint was intended to identify people for whom monthly ibandronate might be a more satisfactory therapeutic option. It is not a measure of comparative bone outcomes or of a treatment effect relative to a control group.

The registry record does not report the observed percentage, the number of participants answering “yes,” or the number included in the primary analysis. It also does not report how incomplete questionnaires were handled. Consequently, the endpoint’s definition is available, but its numerical result and precision cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a participant-level binary classification based on the Candidate Identification Questionnaire. A participant is counted as meeting the endpoint if at least one of the three questions receives a “yes” response. The endpoint is then expressed as a percentage of the specified Part A population. In general, binary outcomes reduce each participant’s response to one of two categories, which can make a result easy to interpret but can conceal variation among the underlying questions.

What does the primary percentage represent?

The outcome concerns the fraction of eligible questionnaire completers who endorsed one or more specified experiences or preferences. It is not the percentage who preferred monthly dosing alone, because stomach upset or missed doses could also qualify a participant. The record does not report the separate response frequency for each question or their overlap. It also does not state how an unanswered questionnaire item was treated when the other items were answered.

The primary endpoint is descriptive rather than a between-group effect estimate. There is no randomized allocation or concurrent comparator in this single-group study. In general, a comparison of outcomes before and after a treatment switch can be affected by factors that change over time, as well as expectations and selection. Without a suitable comparison group, the observed response cannot separate those influences from the effect of treatment.

How should uncertainty be considered?

In general, a confidence interval expresses statistical uncertainty around an estimate under a stated model and analysis. A narrow interval indicates greater precision under those assumptions, while a wide interval indicates less precision. Precision is not the same as freedom from bias: an estimate can be precise while still affected by selection, measurement, or design limitations. The registry record does not report a primary outcome estimate or confidence interval, so neither the observed response nor its precision can be evaluated.

For a percentage based on individual responses, interpretation depends on a clearly stated analysis population and denominator. The registry names all enrolled participants who completed Part A as the primary population, but it does not report the number who completed Part A or the number contributing to the endpoint. It also does not describe missing questionnaire handling. As a result, the relationship between enrollment and the primary analysis denominator is not available.

What does the design imply for the analysis?

The listed design is open and single group, with allocation recorded as not applicable. The study therefore does not support a randomized comparison between monthly ibandronate and continued daily or weekly treatment. The initial regimen is part of the participants’ treatment history and the context for questionnaire responses; it is not a control arm with contemporaneous outcome measurement under an assigned comparison.

Part B participants received monthly ibandronate for up to 6 months. Some secondary outcomes refer specifically to the end of 6 months, including satisfaction and compliance. In general, repeated measurement can describe changes within participants, but a within-participant change alone does not establish that treatment caused the change. The registry record does not provide numerical secondary results or details of the analysis used for repeated measurements.

What can be inferred from the sample-size information?

The study summary gives a target sample size of 500+ individuals, and the registry reports enrollment of 677. The rationale for the target, including any formal power calculation, is not reported in the registry record. The record includes no analysis entries. It therefore does not establish what effect size the study was planned to detect, whether the target was tied to a particular endpoint, or how many participants were expected to contribute to each analysis.

In general, a sample-size calculation depends on assumptions about the outcome, the effect of interest, the significance level, allocation, and analysis method. A planning illustration based on an observed effect is not the trial’s original design justification, and it is not observed power. No numerical outputs from such an illustration are reported in the registry record. They should not be interpreted as evidence that the study had adequate precision for any particular endpoint.

The record does not state whether interim analyses were planned or performed, how multiplicity across outcomes was handled, or which statistical tests and models were used. Those omissions prevent a fuller assessment of the inferential procedures. General statistical principles can clarify what the outcome means, but they cannot replace unreported analytic details or numerical results.

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("Ibandronate")
n      <- c(677)
events <- c(461)
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  Ibandronate  677  461  68.1  64.4  71.6  64.5  71.5  64.5  71.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes in addition to the primary questionnaire endpoint. These include eligibility and entry into Part B, satisfaction after 6 months, compliance with monthly doses, use of reminders, gastrointestinal symptoms, satisfaction by age and activity level, and questionnaire domain scores. When a study examines multiple outcomes, general statistical practice considers how the chance of false-positive findings is managed across those analyses. The registry record does not report a multiplicity strategy, a hierarchy among secondary outcomes, or whether any outcomes were designated as exploratory.

The registry record lists no analysis entries. It does not report a statistical analysis plan, the tests or models used, or whether any interim analyses took place. These details are therefore not reported in the registry record; their absence should not be taken as evidence that a particular procedure was or was not used outside the record.

The primary population is described as all enrolled participants who completed Part A. The registry does not report the number of Part A completers, the number with complete responses, or the handling of missing questionnaire items. It also does not describe missing-data methods for the Part B outcomes. In general, missing-data handling matters because an analysis limited to participants with complete observations can differ from one that uses other assumptions or methods.

Analysis populations for the secondary outcomes, including whether they include all enrollees or only participants who entered Part B, are not fully described in the registry record. The record also does not explain the difference between 677 enrolled participants and the 640 participants at risk listed for safety. Without these details and numerical endpoint results, the impact of missing data, exclusions, or differing analysis populations cannot be assessed.

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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pericarditis (0.2%), iridocyclitis (0.2%), abdominal pain upper (0.2%), hiatus hernia (0.2%), pyrexia (0.2%).

The registry lists 640 participants at risk in the ibandronate group. Among them, 6 were affected by serious adverse events and 18 by other adverse events. The registry also lists six serious adverse event terms, each reported as 0.2%: Pericarditis, Iridocyclitis, Abdominal pain upper, Hiatus hernia, Pyrexia, and Postoperative hernia. The record does not report deaths for this group.

These figures describe events recorded in the study; they do not compare ibandronate with another treatment. Because the trial is single group and has no concurrent control, the counts cannot establish whether event frequency was higher or lower than it would have been under another regimen. The registry record does not provide further detail about event timing, duration, severity beyond the serious-event classification, or attribution to treatment.

The number at risk for safety is 640, while overall enrollment is 677. The registry record does not explain this difference or specify the safety analysis population further. The percentages attached to serious-event terms are reported as listed, and should not be treated as independent of one another or summed. The registry does not state whether a participant could have experienced more than one listed event.

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

BONCURE asks whether current daily or weekly bisphosphonate users reported at least one reason that monthly ibandronate might be a more satisfactory option. Its primary endpoint combines a preference for monthly dosing with reports of stomach upset and missed doses. It is therefore a measure of questionnaire responses and potential treatment preference, not a direct measure of comparative clinical benefit.

The study’s single-group, open design describes a switch to monthly ibandronate without a concurrent randomized control. It can provide a framework for describing participants’ experiences, but the registry record does not report the numerical primary result or numerical secondary results. Consequently, it is not possible to quantify the proportion meeting the primary endpoint, the change in satisfaction, or the frequency of the listed Part B outcomes from this record.

The registry lists safety counts for the ibandronate group, including serious and other adverse events. Without a control group and fuller event detail, those counts do not establish comparative safety or causal attribution. The record also does not report the primary endpoint’s uncertainty, missing-data handling, or analysis methods, limiting assessment of precision and robustness.

In general, preference and satisfaction outcomes can answer questions about participants’ reported experiences, while comparative effectiveness questions require an appropriate comparison and outcome data. This registry record describes the study’s objectives and design but does not provide the numerical outcome evidence needed to assess the size or precision of its findings. It neither demonstrates nor rules out a treatment effect on clinical outcomes.

14. Why This Trial Matters Statistically

This trial is statistically notable because its primary outcome is a composite questionnaire indicator rather than a comparison of clinical outcomes between assigned treatments. Participants could meet the endpoint through any of three distinct responses: a preference for monthly dosing, stomach upset, or missed doses. Combining them gives a broad indicator of potential suitability, but it obscures which experience led to a “yes” response unless the component results are also reported.

The study also illustrates the distinction between a treatment history and a control group. Participants entered while taking daily or weekly therapy, then eligible participants switched to monthly ibandronate. Their prior regimen supplies context, but it is not a randomized concurrent comparator. This design can support descriptive questions about preferences and experiences, while offering limited grounds for attributing changes to the switch.

Transparency about analysis populations, missing responses, and statistical methods is important when outcomes rely on questionnaires and follow-up. The registry identifies the primary population in broad terms but does not report its analysis denominator or missing-data procedures. It also lists several secondary outcomes without reporting their numerical results or how multiplicity was handled. These omissions make it difficult to assess precision and the strength of any statistical claims.

Finally, the record reports safety counts but no comparative safety estimate. Distinguishing descriptive event reporting from comparative inference is essential when reading results from a single-group study. In this case, the registry record makes the research question and design identifiable, but its lack of numerical outcome results prevents assessment of the size and uncertainty of the response.

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 principal limitation for interpreting this registry entry is that numerical results for the primary and secondary outcomes are not reported in the registry record. Without those results, the response rate, satisfaction outcomes, compliance, symptom changes, and questionnaire scores cannot be quantified. No confidence intervals or other precision measures for the primary outcome are reported either.

The open, single-group design has no concurrent randomized comparator. Participants’ prior daily or weekly therapy is not a control arm, and the record does not describe a comparison that could separate treatment effects from expectations, time trends, or other influences. Part B participation followed the Candidate Identification Questionnaire process, so outcomes among Part B participants may not describe all enrolled participants; the registry does not report the numerical flow from Part A to Part B.

The primary endpoint pools three different questionnaire items, and item-specific results are not reported. The record does not explain how incomplete responses were handled or provide the number of participants contributing to the primary analysis. It also does not report the analysis populations or missing-data procedures for the secondary outcomes, statistical methods, interim analyses, multiplicity handling, or a formal sample-size justification.

There is a difference between overall enrollment of 677 and the 640 participants listed as at risk for safety, but the registry record does not explain it. The treatment duration is described as anticipated 3-12 months in the brief summary and as up to 6 months in the arm description; the record does not clarify the difference. Safety event details are limited, and no concurrent control is available for comparison. These limitations constrain assessment of both outcome precision and causal interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: BONCURE Study: A Study of Monthly Bonviva (Ibandronate) in Women With Post-Menopausal Osteoporosis on Bisphosphonate Therapy. — NCT00545779.
• Registry record last updated 2016-10-28; status last verified 2016-09.
• Results first posted 2016-10-28.
• 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

BONCURE (NCT00545779) is a completed, Phase 3, open, prospective, multicenter, two-part, single-group study sponsored by Hoffmann-La Roche. It enrolled 677 participants and examined monthly oral ibandronate among women with postmenopausal osteoporosis who had been using daily or weekly bisphosphonate therapy.

The primary endpoint was the percentage of Part A participants answering “yes” to at least one of three Candidate Identification Questionnaire questions about dosing preference, stomach upset, and missed doses. Part B participants received a 150 mg ibandronate tablet once monthly for up to 6 months. There was no concurrent control group and no masking.

The registry reports 640 participants at risk for safety, with 6 affected by serious adverse events and 18 by other adverse events. Numerical results for the primary and secondary outcomes, the analysis methods, and missing-data procedures are not reported in the registry record.