BAY 0 9867 Cipro Pediatric Use Study (QUIP): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for BAY 0 9867 Cipro Pediatric Use Study (QUIP) (NCT00761462), a non-randomized phase 3 study. The primary outcome is Incidence of Arthropathy (Cumulative).

2. Clinical Question

This was a safety surveillance study, not a randomized comparison designed to isolate a treatment effect. The record describes objective and subjective musculoskeletal evaluations and says the study sought to compare musculoskeletal findings between children receiving ciprofloxacin and those receiving a non-quinolone antibiotic. It also frames these observations in relation to the natural occurrence of musculoskeletal conditions in the general pediatric population. However, the study groups were not randomly assigned, and the comparator group is not a like-for-like control by design. The comparison therefore cannot, by itself, establish that any difference in observed outcomes was caused by the antibiotic received.

The primary endpoint was cumulative arthropathy incidence at 4-6 weeks after treatment, 1 year after treatment, and 2 or 5 years after treatment. The registry says each cumulative incidence includes participants counted at a previous time point plus newly identified cases. The numerical counts at those time points are not reported in the registry record. The clinical question can therefore be described from the registered endpoint definition, but the primary outcome contrast cannot be quantified from the registry information available.

3. Trial Design

The registry classifies this study as Phase 3, but its design is observational: prospective, open-label, non-randomized, naturalistic, and intended for long-term safety surveillance. It has a parallel-group model and no masking. These labels describe different features of the study; the Phase 3 classification does not make the treatment allocation randomized or make the groups directly comparable in the way a randomized trial would.

The study compared pediatric patients receiving ciprofloxacin with patients receiving a non-quinolone antibiotic for infectious diagnoses. Both groups could receive oral suspension, oral tablets, sequential intravenous therapy followed by oral therapy, or intravenous therapy alone. The registry gives total enrollment as 1029. It identifies Bayer as sponsor and records the study as completed, with a start date of 1999-10 and primary completion date of 2008-01.

Follow-up differed between groups: the ciprofloxacin group was followed for 5 years and the non-quinolone antibiotic group for 2 years. The primary endpoint timeframe also includes assessments at 4-6 weeks after treatment and 1 year after treatment, as well as at 2 or 5 years after treatment. The registry does not explain why follow-up durations differed or provide the participant flow at each assessment. With different follow-up periods, the longer-term observation windows are not identical across groups. That matters when interpreting cumulative event counts, because participants observed for different lengths of time have different opportunities for an event to be identified.

Allocation was non-randomized. The registry does not report how clinicians or participants selected a treatment, or whether treatment choice was related to diagnosis, illness severity, prior treatment, or other factors. These details are important in observational comparisons because group characteristics may differ before treatment begins. Open-label status means the study was not masked, but the record does specify that an independent safety committee reviewed musculoskeletal-event data and decided whether each patient had arthropathy. The committee’s independent assessment is part of the endpoint definition; it does not remove possible differences in treatment selection, follow-up, or event detection.

The registry reports two outcome measures and zero analyses. The primary endpoint is described, but its numerical results are not reported in the registry record. The record also does not report a detailed statistical analysis plan, sample-size justification, or procedures for handling incomplete follow-up.

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: The decision to treat with ciprofloxacin or a non-quinolone antibiotic was made prior to a patient's enrollment in the study and was based on the particular infection, type of patient, medical history, and the clinical evaluation by the prescribing physician. The study was not randomized.

Treatment

Reasons for not completing this period:

2 or 5 Years Long-term Safety Follow-up

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients valid for safety (all patients confirmed to have received at least one dose of study drug)

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 Incidence of Arthropathy (Cumulative), measured over 4-6 weeks after treatment / 1 year after treatment / 2 or 5 years after treatment.

The primary endpoint is cumulative incidence of arthropathy, measured as the number of participants classified as having arthropathy. An independent safety committee reviewed musculoskeletal-event data and decided whether each patient had arthropathy or not. The listed assessment windows are 4-6 weeks after treatment, 1 year after treatment, and 2 or 5 years after treatment. The registry explains that the count at each time point includes cases counted at the previous time point as well as newly identified patients.

This kind of endpoint is used to describe how many participants have experienced an event over follow-up. A cumulative count can show the growing total of identified cases across successive assessments, provided the relevant population and observation period are clear. It is not the same as a count of only newly occurring cases at each individual visit. The registry does not provide the actual counts at the stated time points, so the extent or timing of the observed cumulative arthropathy cannot be assessed from the record.

The endpoint is clinically focused on musculoskeletal events, consistent with the study’s stated safety-surveillance objective. The registry specifies that the population was patients valid for safety, defined as all patients confirmed to have received at least one dose of study drug. It does not report the number assessed at each time point, the number with incomplete follow-up, or additional detail on the committee’s decision criteria. Those details would help readers understand how the endpoint was applied and how complete the cumulative counts are.

The registry also notes that the 112/20 arthropathies are mentioned in the other Adverse Events section. This cross-reference does not give the numerical primary endpoint results at the specified assessment windows or clarify how those figures relate to each time point. The endpoint definition is therefore available, while its time-specific results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes an observational comparison with a binary primary endpoint recorded as participant counts. It does not report inferential analyses for that endpoint. The concepts below are general explanations of how such data and study designs are usually interpreted; they are not claims about unreported methods used in this study.

What does a binary participant count represent?

In general, a binary outcome classifies each participant into one of two states, such as event or no event. The registry defines arthropathy in this way: the independent safety committee decided whether each patient had arthropathy or not. A count of participants with an event is descriptive. To interpret it as a proportion, readers also need the relevant denominator: the number of participants assessed in the group at the specified time. For comparisons over time, it is important to know whether participants remained under observation and whether the denominator changed. The registry defines the safety population as patients who received at least one dose, but does not provide time-specific denominators for the primary endpoint.

What does cumulative incidence mean in this record?

The record explicitly defines each incidence count as including patients shown at the previous time point plus any newly identified patients with the event. In general, cumulative event counts represent the total identified up to a point in follow-up rather than only new events since the previous assessment. This distinction matters: a cumulative count should not be interpreted as an interval-specific count. It also does not, by itself, describe the probability of an event unless the relevant population and follow-up are accounted for. The registry’s endpoint definition is available, but its numerical counts are not reported in the registry record.

Why does non-randomized allocation matter?

In general, random assignment aims to balance measured and unmeasured baseline characteristics between treatment groups, on average. In an observational study, treatment is not assigned randomly, so the groups can differ in clinical or other characteristics that may also relate to the outcome. This is a source of confounding: an observed group difference may reflect treatment, differences between the patients, or both. The registry identifies allocation as non-randomized and says the arms are not a like-for-like control comparison. It does not report the treatment-selection process, baseline balance, adjustment variables, or an adjusted primary analysis. Therefore, the record does not establish that a group difference would be attributable to the antibiotic.

How should unequal follow-up be considered?

In general, participants observed for different lengths of time have different opportunities for an event to occur or be detected. Cumulative counts can be misleading in a direct comparison if follow-up differs and the analysis does not account for time under observation. Time-to-event methods can address differing follow-up in some settings, but their appropriateness depends on assumptions and adequate event and censoring information. The registry records 5 years of follow-up for the ciprofloxacin group and 2 years for the non-quinolone group. It does not report a time-to-event analysis, censoring details, or an explanation for the difference in follow-up. No particular analysis method should be inferred.

What do confidence intervals and p-values add?

In general, a confidence interval describes the range of effect estimates compatible with the data and the statistical method, and communicates uncertainty around an estimate. A p-value, when calculated under a specified model and null hypothesis, describes how unusual the data would be under that null model. Neither measure resolves confounding in a non-randomized study, and neither substitutes for clear outcome definitions or denominators. The registry does not report a primary endpoint estimate, confidence interval, or p-value. It is therefore not possible to assess the statistical precision or statistical evidence for a primary endpoint contrast from the registry record.

What does the safety population mean?

The primary endpoint population is described as patients valid for safety: all patients confirmed to have received at least one dose of study drug. This definition identifies a population based on exposure rather than reporting the number with complete endpoint data. In general, an analysis population and the number actually assessed at each time point can differ when follow-up or outcome information is incomplete. The registry does not report time-specific analysis populations or the handling of missing assessments. The adverse-event figures separately list numbers at risk for each group; those counts should be read as the denominators attached to those reported adverse-event entries, not assumed to be the denominator for every primary endpoint assessment.

What can a planning illustration tell readers?

In general, sample-size planning asks how many participants would be needed under stated assumptions to detect a chosen effect with specified statistical error rates. Such an illustration is not an observed result and does not describe the power achieved by a completed study. The stated planning approach for this record uses a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a fraction of an observed effect; time-to-event planning uses a total event count. Those are planning assumptions, not evidence that the study itself used those design choices. The registry does not report its own sample-size justification or detailed statistical design rationale. The observed primary effect needed to interpret an effect-based illustration is not reported in the registry record.

Overall, the statistical information permits a clear description of the registered design and endpoint, plus a descriptive reading of the listed adverse-event counts. It does not permit a primary endpoint comparison with an estimate of effect or precision. No unreported test, adjustment, missing-data procedure, interim analysis, or model should be assumed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists two outcome measures and zero analyses. It identifies cumulative arthropathy incidence as the primary endpoint, but the numerical results for that endpoint are not reported in the registry record. The record does not explain whether additional outcomes were tested, how a primary analysis was selected, or whether any adjustment for multiple comparisons was planned or used. Multiplicity refers, in general, to the increased chance of a false-positive finding when several hypotheses are tested. Whether that issue arose in this study cannot be determined from the registry information.

The record defines the primary endpoint safety population as all patients confirmed to have received at least one dose of study drug. It does not report how many participants had evaluable arthropathy information at each follow-up point, how many were lost to follow-up, or how incomplete assessments were handled. It also does not describe imputation, sensitivity analyses, or assumptions about missing outcomes. These omissions matter because cumulative event counts depend on knowing who was assessed and over what period.

The adverse-event entries include group-specific numbers at risk and affected participants, but the registry does not state in the available information how missing adverse-event data were handled. Death counts are not reported in the registry record. The record also does not report an interim-analysis plan, stopping rules, or a detailed statistical analysis plan. Those methods should not be inferred from the observational design or from the outcome descriptions.

For this study, the difference in follow-up duration is especially relevant to missingness and outcome availability: the ciprofloxacin group was followed for 5 years and the non-quinolone group for 2 years. The registry does not explain how those windows relate to participants’ completeness of follow-up or how time under observation was incorporated into any analysis. In the absence of those details and the primary endpoint results, readers cannot assess how missing information or multiple analyses may have influenced comparative conclusions.

11. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pyrexia (0.8%), neutropenia (0.6%), acute lymphocytic leukaemia (0.6%), clostridium difficile colitis (0.4%), otitis media (0.4%).

The registry lists serious adverse events separately from other adverse events. In the ciprofloxacin group, 25 participants were affected by serious adverse events among 487 at risk; 206 were affected by other adverse events among 487 at risk. In the non-quinolone antibiotic group, 6 participants were affected by serious adverse events among 507 at risk; 76 were affected by other adverse events among 507 at risk. These are the counts and denominators reported in the registry. They are descriptive entries, not estimates of a causal treatment effect.

The registry also lists serious adverse-event terms with percentages: Pyrexia, 0.8%; Neutropenia, 0.6%; Acute lymphocytic leukaemia, 0.6%; Clostridium difficile colitis, 0.4%; Otitis media, 0.4%; and Sepsis, 0.4%. The record does not identify a treatment group alongside each term in the information, so these terms should not be assigned to either group. Death counts are not reported in the registry record.

In general, adverse-event counts depend on how events were defined, collected, and followed up. The registry record identifies the serious and other adverse-event counts but does not provide uncertainty intervals or a statistical comparison for these entries. Since treatment allocation was non-randomized and follow-up differed between groups, the counts should not be read as a like-for-like comparison. The serious adverse-event figures do not replace the missing numerical results for the primary arthropathy endpoint.

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

The registry record establishes that a prospective, open-label, non-randomized safety surveillance study compared pediatric patients receiving ciprofloxacin with patients receiving a non-quinolone antibiotic. It defines cumulative arthropathy as the primary endpoint and describes independent safety committee review. It also reports adverse-event counts for each group. These details show the intended focus and some of the safety information recorded for the study.

The record does not report the numerical primary endpoint results at 4-6 weeks after treatment, 1 year after treatment, or 2 or 5 years after treatment. It therefore does not show how many participants were classified with arthropathy at those time points, the magnitude of any group difference, or the uncertainty around a comparison. The listed adverse-event counts do not fill that gap because they concern other event categories and are not a reported statistical comparison of the primary endpoint.

The design also limits what a group contrast could mean. In general, observational treatment groups may differ before treatment because allocation is not random. This study’s registry record explicitly notes that the arms are not a like-for-like control comparison. The available information does not describe adjustment for baseline differences or other potential confounding. The registry also gives different follow-up durations for the groups, which affects the opportunity to observe events. These features make a causal interpretation especially uncertain.

Accordingly, the record can be used to describe the study design, endpoint definition, follow-up periods, safety population definition, and listed adverse-event counts. It cannot establish from the information reported whether ciprofloxacin caused more or fewer arthropathy events than the comparator, nor can it establish the precision of such a comparison. The absence of primary endpoint results in the registry record is not evidence that no events occurred; it means the numerical results needed to evaluate the endpoint are not reported there.

This interpretation concerns the information in the registry record, not a clinical recommendation. No treatment conclusion should be drawn from the descriptive safety entries alone. A complete comparative assessment would require clearly reported primary endpoint counts or estimates, relevant denominators and follow-up information, and the analysis methods used to address the non-randomized design and differing observation periods.

13. Why This Trial Matters Statistically

This study is statistically instructive because it combines a defined safety endpoint with an observational treatment comparison. The primary endpoint is described in concrete terms: an independent safety committee classified whether each patient had arthropathy, and the registry explains that later cumulative counts include earlier cases plus newly identified cases. That definition helps distinguish cumulative counts from new events at an individual visit. At the same time, the numerical endpoint results are not reported in the registry record, illustrating why a clear endpoint definition alone is not enough to judge a study’s findings.

The non-randomized allocation is another central statistical feature. In general, an observed difference between treatment groups can reflect differences in patients or care as well as treatment. The registry itself cautions that the arms are not a like-for-like control comparison. For clinical researchers, this is a reminder to separate descriptive group comparisons from causal claims, and to look for information about baseline characteristics, treatment selection, confounding control, and sensitivity analyses. The registry does not report those analysis details.

The unequal follow-up periods also matter. The ciprofloxacin group was followed for 5 years, while the non-quinolone antibiotic group was followed for 2 years. Cumulative event counts collected over unequal windows do not represent equal observation opportunities. A comparative interpretation needs clear time-specific denominators and methods that account for follow-up; the registry does not report those methods for the primary endpoint.

Finally, the record provides some adverse-event counts but no primary endpoint analysis. This distinction is useful when reading trial registries: an endpoint can be registered and defined without its numerical results being reported, and descriptive safety entries do not substitute for the missing primary comparison. The study therefore highlights the importance of transparent outcome reporting, analysis details, and careful limits on inference in observational safety research.

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 most consequential limitation of the registry information is that numerical results for the primary cumulative arthropathy endpoint are not reported in the registry record. Although the endpoint, assessment windows, and safety population are described, the record does not give the event counts at those time points or a comparative estimate. It also does not report confidence intervals or a p-value for the primary endpoint.

The non-randomized design means the treatment groups may have differed in relevant ways. The registry does not describe how treatment was selected, the groups’ baseline characteristics, or any adjustment for confounding. It explicitly cautions that the arms are not a like-for-like control comparison. Thus, even if a numerical difference were available, the record would not establish from its reported methods that the difference was caused by treatment.

Follow-up duration differed: 5 years for ciprofloxacin and 2 years for non-quinolone antibiotics. The registry does not explain the reason for this difference or report how it was handled analytically. It also does not give time-specific denominators, completeness of follow-up, or missing-data procedures for the primary endpoint. These omissions limit interpretation of cumulative counts and comparisons across groups.

The independent safety committee’s role is described, but the registry does not provide detailed adjudication criteria or information about how disagreements and incomplete records were handled. The adverse-event section gives counts and a list of serious-event terms, but does not report uncertainty intervals or a statistical comparison. Death counts are not reported in the registry record.

Finally, the registry does not report a detailed statistical analysis plan, a trial-specific sample-size justification, interim analyses, or multiplicity procedures. The record identifies two outcome measures and zero analyses. These limitations describe gaps in the registered information; they do not establish that unreported procedures or results did not exist elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: BAY 0 9867 Cipro Pediatric Use Study (QUIP) — NCT00761462.
• Registry record last updated 2015-07-31; status last verified 2015-07.
• Results first posted 2009-04-14.
• 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.

18. Record Summary

NCT00761462, titled BAY 0 9867 Cipro Pediatric Use Study (QUIP), is recorded as a completed Phase 3 study sponsored by Bayer. The registry describes it as a prospective, open-label, non-randomized, naturalistic, long-term safety surveillance study in pediatric patients with infectious diagnoses. Total enrollment is 1029. The study compared ciprofloxacin with a non-quinolone antibiotic, with follow-up listed as 5 years for the ciprofloxacin group and 2 years for the comparator group.

The primary endpoint was cumulative incidence of arthropathy, assessed by an independent safety committee among patients confirmed to have received at least one dose. Assessment timeframes were 4-6 weeks after treatment, 1 year after treatment, and 2 or 5 years after treatment. Numerical primary endpoint results and analyses are not reported in the registry record. The record lists group-specific serious and other adverse-event counts, but the non-randomized design and unequal follow-up limit direct comparative interpretation.