Compliance And Safety Study In Children With Upper And Lower Respiratory Tract Infections: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Compliance And Safety Study In Children With Upper And Lower Respiratory Tract Infections (NCT00939185), a registered phase not stated study. The primary outcome is Number of Patients With Adverse Events (AEs).

2. Clinical Question

The study objective was to collect information about safety, tolerability and compliance with azithromycin in children with bacterial infections of the upper and lower respiratory tract. The primary outcome was the number of patients with adverse events, with events recorded 3 to 7 days after receiving treatment. The adverse-event definition included observed or volunteered events, regardless of whether a causal relationship to the study treatment was suspected.

Other listed outcomes concern withdrawal from the study, compliance, and the time from hospital entry to consultation and diagnosis. Results for these outcomes are not reported in the registry record. Consequently, the stated objective extends beyond the results available for interpretation: the adverse-event counts can be described, but the registry record does not permit a quantitative assessment of compliance or the other secondary outcomes.

3. Trial Design

The registry record identifies this as a completed study sponsored by Pfizer. It lists an enrollment of 400, a start in 2007-04 and primary completion in 2009-01. The condition is respiratory tract infections, and the study intervention is azithromycin. The brief summary describes children with bacterial infections of the upper and lower respiratory tract.

The record does not state that participants were randomized. Allocation is not stated, and the available adverse-event results do not establish a like-for-like control group. It would therefore be inappropriate to interpret the listed group as one side of a randomized comparison or to attribute differences to treatment. The registry record does not report a comparator regimen or an allocation procedure.

The primary outcome is the number of patients with adverse events, with a timeframe of 3 to 7 days after receiving treatment. The safety population was defined by known receipt of at least one dose. People who were dispensed study treatment and immediately lost to follow-up were not included among those known to have been dosed.

The registry lists withdrawal, compliance and time from hospital entry to consultation and diagnosis as secondary outcomes. It records four outcome measures and no analyses. Results for the listed secondary outcomes and a statistical analysis plan are not reported in the registry record. The stated enrollment is not, by itself, evidence of a particular sample-size justification or a comparative design. The protocol, planned analysis, and reasons for the size of the safety population are not reported in the registry 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 population = Those subjects who were known to have received at least one dose of the study treatment. Subjects who were dispensed study treatment and immediately lost to follow-up were not included among those known to have been dosed.

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 Patients With Adverse Events (AEs), measured over 3 to 7 days after receiving treatment.

The primary endpoint is the number of patients with adverse events. It counts people affected rather than the total number of event episodes. The stated assessment timeframe is 3 to 7 days after receiving treatment. Events could be observed or volunteered, and the definition did not require investigators to suspect that the study treatment caused them.

This type of outcome is used to describe how often participants are recorded as having at least one event during a specified period. For interpretation, the count must be read alongside the number of people assessed. The adverse-event results list an Azithromycin group with 390 at risk. They report 27 affected by other adverse events and 0 affected by serious adverse events. These are descriptive counts; they do not establish whether the event frequency differs from what would have occurred under another treatment or without treatment.

In general, a participant-level endpoint can be useful for safety monitoring because it distinguishes people with an event from those without one. It does not describe how many events each affected person experienced, their duration, severity beyond the serious classification, or their clinical course. Those details are not reported in the registry record. Nor does the endpoint alone establish causality: the study definition explicitly included events regardless of suspected causal relationship to the investigational product.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record specifies a participant count as the primary outcome, rather than an event rate, time-to-event measure or continuous measurement. For this kind of endpoint, each person is classified according to whether an adverse event was recorded within the stated timeframe. The resulting group count can be described alongside the number at risk. In this study, the record lists 390 at risk in the Azithromycin group and reports 27 affected by other adverse events and 0 affected by serious adverse events.

What does a participant count tell the reader?

In general, a participant-level event count answers whether people were recorded as having an event, not how many event episodes occurred. A person with several events may still contribute as one affected participant to this endpoint. The registry record does not give event-level counts or explain how repeated events were handled in the posted endpoint result. The count also depends on how events were identified and collected. Here, the stated definition includes observed or volunteered events regardless of suspected causal relationship to the investigational product.

The endpoint is bounded by its stated observation period, 3 to 7 days after receiving treatment. In general, an event count over a defined period is interpretable only with attention to who was observed and for how long. The registry record defines the safety population as subjects known to have received at least one dose. It excludes from that known-dosed group subjects who were dispensed study treatment and immediately lost to follow-up. Further details of follow-up completeness are not reported in the registry record.

Why is a comparison not justified?

A treatment comparison requires groups whose outcomes can meaningfully be contrasted under the design and analysis used. The record does not state the allocation procedure, and the adverse-event listing shows an Azithromycin group without an established like-for-like control group. General statistical principle: when treatment assignment is not documented as randomized, observed differences between groups, if any, could reflect differences in who entered each group, how they were followed, or other factors, rather than treatment itself. In this case, the listed results do not supply a control comparison from which to estimate a treatment effect.

No analysis results are listed in the registry record. It does not report a confidence interval or hypothesis test for the primary endpoint, an adjusted model, or an analysis plan. General statistical principle: a confidence interval communicates uncertainty in an estimate under a particular model, while a p-value addresses compatibility with a specified null hypothesis under the test assumptions. Neither can be reconstructed as a reported study result without the relevant method and result. No such values should be inferred from the counts alone.

How should the planning illustrations be understood?

The planning assumptions describe an illustration computed from the observed effect, not the study's own design justification. The illustration uses a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation; the effect to detect is a stated fraction of the observed effect. These assumptions describe hypothetical planning, not the allocation or analysis actually used in this study. The registry record does not report the protocol's sample-size justification.

Any resulting sample-size value is a planning illustration, not evidence of observed power. General statistical principle: power is a design property calculated under assumed effects, variability and analysis conditions; it is not a retrospective measure of whether a completed study found a result. The record does not list numeric planning estimates in the registry record for interpretation, so no particular planning requirement can be stated. Nor can the stated enrollment be treated as confirmation that the study had adequate power for its safety endpoint.

For a binary participant outcome, statistical methods often model the probability that a participant has at least one event. That general description does not mean that such a model was fitted; no analysis is listed. The registry record also does not report adjustments for covariates, approaches to repeated events, or methods for accounting for incomplete observation. Such choices can affect estimates and uncertainty, and their absence from the record limits statistical interpretation.

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("Azithromycin")
n      <- c(390)
events <- c(27)
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  Azithromycin  390  27  6.9  4.6  9.9  4.8  9.9  4.8  9.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures, including the primary outcome and the listed secondary outcomes of withdrawal, compliance, and time from hospital entry to consultation and diagnosis. It does not report a multiplicity plan, such as a hierarchy of hypotheses or an adjustment for testing several outcomes. No analyses are listed. The secondary outcome results are not reported in the registry record, so there is no basis for assessing their statistical significance or for determining whether any multiplicity procedure was used.

Missing-data methods are not reported in the registry record. The primary outcome is framed as a count of patients with adverse events during 3 to 7 days after treatment, but the record does not state how incomplete observation or unknown event status was handled. The safety-population definition does explain that subjects had to be known to have received at least one dose. Subjects dispensed treatment and immediately lost to follow-up were not included among those known to have been dosed. That definition does not, by itself, establish how missing outcome information among the safety population was treated.

The record states an enrollment of 400 and lists 390 at risk for the adverse-event results. These figures describe different registry entries; the record does not report a complete account of why they differ or whether the same observation status applied to every outcome. It would be inappropriate to infer the reasons for non-inclusion or to assume that all secondary outcomes had the same available population.

The analysis population for the reported adverse-event counts is described as the safety population. A separate intention-to-treat analysis population is not reported in the registry record. The record also does not describe imputation, sensitivity analyses, interim analyses, or a prespecified missing-data strategy. Without these details, the robustness of outcome estimates to incomplete follow-up cannot be evaluated.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event result is 0 affected in the Azithromycin group among 390 listed at risk. The other-adverse-event count is 27 affected in that group. These are observed counts, not estimates from a comparative analysis. The registry record does not establish a control group for comparing serious-event counts.

A zero observed serious-event count means that no participants were recorded as affected by serious adverse events in the posted result. General statistical interpretation: a zero count does not prove that the underlying probability of a serious event is exactly zero. The precision of that conclusion would ordinarily be expressed with an interval under a stated method, but no such interval is reported in the registry record. The count also applies to the defined safety population and observation framework, not necessarily to every person enrolled or to a longer period of observation.

The adverse-event definition included events regardless of suspected causal relationship to the study treatment. Therefore, neither the serious-event count nor the other-event count should be described as treatment-caused events. The record does not provide detailed event terms, severity beyond serious classification, or outcomes after an event was recorded. The safest reading is descriptive and limited to the group, population definition and timeframe stated in the registry.

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

The result provides a description of recorded adverse events in the Azithromycin group. The registry lists 390 at risk, with 27 affected by other adverse events and 0 affected by serious adverse events. The event definition includes observed and volunteered events regardless of suspected causal relationship, and the stated timeframe is 3 to 7 days after receiving treatment. This information characterizes the posted safety results within those boundaries.

It does not establish that azithromycin caused or prevented any event. The registry record does not establish a like-for-like control comparison, and no statistical analysis is listed. The counts cannot be used to estimate a comparative effect or to assess the precision of a treatment difference. A zero count for serious events is not proof that serious events cannot occur, and the record does not report an uncertainty interval for that count.

The study objective also mentions tolerability and compliance, but the registry record does not report results for compliance. It lists withdrawal and time to consultation and diagnosis as secondary outcomes, without posted results for those measures. The primary adverse-event outcome does not answer whether the infection improved, whether a particular regimen is preferable, or whether the treatment is suitable for an individual child.

General statistical principle: findings from an observed group are most directly informative about that group's recorded outcomes under its study conditions. Extending results to other settings requires considering how the participants, care, event collection and follow-up compare. The registry record offers limited detail on those features. Its enrollment figure is not a substitute for outcome-specific population details or uncertainty estimates.

Accordingly, the result should be treated as a descriptive safety record rather than evidence of efficacy, comparative safety, or absence of risk. It answers a narrow counting question for the listed group and does not resolve the broader questions raised by the study objective.

14. Why This Trial Matters Statistically

This study is statistically instructive because its stated primary outcome is a count, while its available results do not support a treatment comparison. Readers may be tempted to interpret an adverse-event count as evidence about whether a treatment is safer or riskier. That inference requires more than a count: it requires an appropriate comparison, a defined analysis and information about uncertainty. The registry record does not establish a like-for-like control group and lists no analyses.

The distinction between enrollment and the safety population also matters. The record states an enrollment of 400, while the adverse-event group lists 390 at risk. Enrollment and outcome-specific analysis populations are not interchangeable. The safety population is defined by known receipt of at least one dose, with a stated exclusion for people dispensed treatment but immediately lost to follow-up when dosing was not known. The record does not fully explain the difference between the enrollment and the listed safety population.

Safety outcomes also depend on their definitions and observation windows. Here, events could be observed or volunteered, regardless of suspected causality, and the stated timeframe is 3 to 7 days after receiving treatment. Those choices shape what the endpoint captures. They do not necessarily describe longer-term events, event frequency per person, or causal attribution.

Finally, the registry lists secondary outcomes but does not report their results. This illustrates why a trial objective and a posted result set are not the same thing. Statistical interpretation must follow the outcomes and analyses actually documented, rather than fill gaps with assumptions. In this record, the strongest defensible reading is descriptive, with substantial limits on comparison and precision.

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 most important limitation is that the registry record does not establish a like-for-like control comparison. Allocation is not stated, and the adverse-event result lists an Azithromycin group. The result therefore cannot estimate a comparative safety effect or separate treatment effects from other explanations.

The record supplies limited detail about the treatment regimen. It identifies azithromycin but does not report dose, schedule or duration. It also gives no detailed description of event ascertainment beyond the statement that observed or volunteered events were reported regardless of suspected causal relationship. Individual event terms, severity gradations beyond serious classification, and event outcomes are not reported.

The observation period for the primary outcome is 3 to 7 days after receiving treatment. The registry record does not report additional follow-up sufficient to characterize events outside that period. Nor does it report the handling of incomplete outcome data, event-specific missingness, or sensitivity analyses. The safety-population definition clarifies who was considered known to have received at least one dose, but does not resolve all questions about follow-up completeness.

The record lists 400 enrolled and 390 at risk for the adverse-event result, but does not fully explain the difference. Results for compliance, withdrawal and time to consultation and diagnosis are not reported in the registry record. No analyses, confidence intervals or p-values are listed, and no multiplicity or missing-data plan is reported. The protocol, sample-size justification and statistical analysis plan are also not reported in the registry record. These gaps constrain both the precision and scope of any interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Compliance And Safety Study In Children With Upper And Lower Respiratory Tract Infections — NCT00939185.
• Registry record last updated 2010-03-30; status last verified 2010-03.
• Results first posted 2010-03-18.
• 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

The registry record describes a completed Pfizer-sponsored study of azithromycin in children with upper and lower respiratory tract infections. It reports enrollment of 400, with the study starting in 2007-04 and primary completion in 2009-01. The primary outcome was the number of patients with adverse events 3 to 7 days after receiving treatment. Events were recorded whether observed or volunteered and regardless of suspected causal relationship.

The adverse-event result lists an Azithromycin group with 390 at risk, 27 affected by other adverse events and 0 affected by serious adverse events. The safety population included subjects known to have received at least one dose. Allocation is not stated, a like-for-like control comparison is not established, and no analyses are listed. Results for the secondary outcomes are not reported in the registry record. Accordingly, the posted results support a descriptive account of adverse-event counts, not a comparative or causal conclusion.