Evaluation of Effectiveness of the Treatment After Repeated Administration of Klacid®SR: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluation of Effectiveness of the Treatment After Repeated Administration of Klacid®SR (NCT01130883), a registered phase not stated study. The primary outcome is Disappearance or Significant Alleviation of Symptoms.

2. Clinical Question

3. Trial Design

This was a prospective, single-arm, single-country, multicenter post-marketing observational study sponsored by Abbott. The registry lists the study as completed, with 3130 participants enrolled. Investigational sites were to include general practitioner consulting rooms, pneumologists, and centers experienced in treating acute infections of the trachea and bronchi, acute exacerbation of chronic bronchitis, and mild community-acquired pneumonia. The study was conducted in the Czech Republic.

Klacid SR was prescribed in the usual manner, according to local market authorization and local guidelines. The objective was to describe the effectiveness of treatment after repeated administration in patients who had received Klacid SR previously, from 6 weeks to 24 months before the dose given during the study. This design records outcomes during routine care rather than assigning participants to treatment groups under a randomized protocol.

The primary endpoint was an overall therapeutic response assessed by the physician as “yes” or “no,” based on symptom disappearance or significant alleviation. The physician also considered objective findings, including auscultation and chest X-ray results when available. The listed assessment period was Day 8 - 16. Secondary outcomes included body temperature, bacteriological investigation when available, cough and its character, dyspnea and its type, auscultation, chest X-ray in cases of community-acquired pneumonia, the position of the study drug in the sequence of antimicrobial treatments, and compliance.

A total of 3130 participants were enrolled, while 3128 were included in the analysis. Two participants were excluded because they did not meet entry criteria: they were less than 18 years of age. The registry record does not report a concurrent control group or an allocation procedure. A sample-size justification, protocol details beyond those described, and a detailed statistical analysis plan 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: A total of 3130 participants were enrolled into the study and 3128 were included in the analysis. Two participants were excluded from the analysis as they did not meet entry criteria (2 participants were less than 18 years of age).

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 Disappearance or Significant Alleviation of Symptoms, measured over Day 8 - 16.

The primary endpoint was the number of participants with a physician-assessed overall therapeutic response. A response was classified as “yes” or “no,” with “yes” reflecting disappearance or significant alleviation of symptoms following treatment. Physicians also considered objective findings, such as auscultation and chest X-ray results when available. The endpoint was assessed during Day 8 - 16.

This kind of endpoint is intended to capture a clinical judgment about the overall course of symptoms rather than a single laboratory measurement. Combining symptom assessment with available objective findings can represent more than one aspect of a patient’s status, but the result remains dependent on the physician’s assessment. The registry record does not report a standardized scoring instrument, rules for resolving variation between assessors, or how unavailable objective findings were handled.

The endpoint is binary: each participant’s response is classified into one of two categories. In general, a binary endpoint can be summarized by the number of participants in each category and, when denominators are available, the proportion in each category. The registry record does not report the number of “yes” or “no” responses, so neither the observed response proportion nor its precision can be described. The stated endpoint and timeframe identify what the study intended to assess, but do not establish the magnitude of the recorded response.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s primary outcome is binary: a physician classified overall therapeutic response as “yes” or “no.” The underlying judgment concerned disappearance or significant alleviation of symptoms after treatment, with objective findings considered when available. In general, binary outcomes are summarized by reporting the count in each category and the denominator used to calculate a proportion. A proportion conveys the observed frequency of a response in the analyzed group; it does not by itself establish that treatment caused the response. The registry record does not report the response counts or a response proportion.

In general, an estimate is more informative when accompanied by a confidence interval. A confidence interval describes the range of values reasonably compatible with the observed data under the chosen statistical model. Its width conveys precision: narrower intervals indicate greater precision, while wider intervals indicate greater uncertainty. The registry record does not report a confidence interval for the primary endpoint, nor does it provide the endpoint estimate needed to interpret one.

A p-value, in general, measures how unusual data would be under a specified null hypothesis and statistical model. It does not measure the size or clinical importance of an effect, and it does not prove that a finding is true or false. Interpreting a p-value requires knowing the comparison, hypothesis, model, and analysis population. No primary endpoint p-value or detailed inferential analysis is reported in the registry record. The absence of a reported p-value is not evidence that a result was or was not statistically significant.

The study is described as prospective, observational, and single-arm. In general, prospective data collection can define when outcomes are assessed, while observational treatment decisions reflect routine care rather than randomized assignment. With no concurrent control group, the study can describe outcomes among treated participants, but it cannot isolate treatment effects from other explanations for those outcomes. Differences in patient characteristics, illness course, and clinical decisions may influence the observed response. These are general limitations of interpreting uncontrolled observational outcome data; the registry does not report analyses designed to adjust for such influences.

The registry’s planning assumptions describe an illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Such assumptions describe a hypothetical planning calculation, not an analysis of observed study outcomes. The study itself is single-arm, and no observed primary endpoint effect is reported in the registry record. Therefore, no specific planning quantity can be interpreted from the available record. A planning illustration is not observed power: it does not tell readers the probability that the completed study detected an effect.

More generally, a sample-size calculation depends on the outcome, the effect considered important or targeted, the variability or event frequency assumed, the statistical test, and the desired error properties. A calculation based on a fraction of an observed effect is a planning scenario rather than a substitute for an estimate and its confidence interval. The registry record does not report the study’s sample-size justification or the values needed to evaluate a study-specific calculation. Enrollment of 3130 participants should not be treated as proof that the study had adequate power for its primary endpoint.

For binary event outcomes, interpretation also depends on the denominator and on how outcomes are counted. A participant count, an event count, and a rate are not interchangeable. If a person can experience more than one event, counting events can differ from counting people with at least one event. The registry safety information gives participants at risk and affected counts, but does not report a comparative analysis. General methods for comparing event frequencies would require a defined comparison and appropriate treatment of the observation structure; neither a control group nor such a comparative analysis is reported.

Over-dispersion is a general issue when observed variation is larger than a statistical model expects. If a model assumes independent outcomes with a particular variance structure but the data vary more widely, standard errors may be too small and confidence intervals too narrow. This matters especially for clustered or repeated observations. The registry describes multicenter data collection and lists multiple outcomes, but it does not report a model, a clustering adjustment, or repeated-measures analysis. It is therefore not possible to say whether over-dispersion was assessed or whether any adjustment was used.

Multiplicity arises when many outcomes or statistical comparisons are examined. In general, the more tests performed, the greater the chance of at least one apparently unusual result under a collection of null hypotheses. Researchers may address this through prespecified outcome hierarchies or adjustments, but the appropriate approach depends on the objectives and analysis plan. The registry lists 11 outcome measures and zero analyses; a multiplicity strategy is not reported in the registry record. No conclusion about adjustment, testing order, or selective reporting can be drawn from the listed information.

Finally, analysis populations and missing data affect what an estimate represents. The record states that 3128 participants were included in the analysis after two people younger than 18 years were excluded for not meeting entry criteria. It does not report whether endpoint information was missing among those analyzed, how missing values were handled, or whether the analyzed population was defined in further detail. In general, complete-case analysis, imputation, and other approaches rely on different assumptions. Without the missing-data plan and outcome completeness, the potential effect of missing information cannot be assessed.

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("Klacid SR Treatment")
n      <- c(3128)
events <- c(3109)
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  Klacid SR Treatment  3128  3109  99.4  99.1  99.6  99.1  99.6  99.1  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary physician-assessed response and secondary measures concerning temperature, bacteriological investigation when available, respiratory symptoms, examination findings, chest X-ray in cases of community-acquired pneumonia, treatment sequence, and compliance. The record does not report a multiplicity plan, such as a hierarchy of outcomes or an adjustment for multiple statistical tests. It also lists zero analyses. Without reported analyses, there is no basis for determining how many comparisons were performed or whether any multiplicity method was used.

The analysis population is described as 3128 participants from 3130 enrolled. Two participants were excluded because they were less than 18 years of age and did not meet entry criteria. This explains the stated exclusions, but it does not describe missing outcome information among the analyzed participants. Whether the primary endpoint was available for all 3128, how missing values were handled, and whether participants were excluded for any other reason are not reported in the registry record.

In general, missing-data methods depend on why information is missing and on assumptions about the unobserved outcomes. Excluding participants with missing outcomes can affect an estimate if those participants differ systematically from those with recorded outcomes. Imputation and other methods also require assumptions and should be described so readers can understand their implications. The registry does not report a missing-data strategy, sensitivity analysis, or a detailed definition of the analysis population beyond the stated age-related exclusions.

A sample-size justification and a detailed statistical analysis plan are not reported in the registry record. Consequently, it is not possible to assess whether the planned analysis addressed the listed outcomes, how the primary endpoint was to be analyzed, or how missing data and multiple outcomes were to be handled.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: tuberculosis pleuritis (0.0%), pulmonary tumor (0.0%).

The registry lists 3128 participants at risk for serious adverse events and reports 2 serious adverse events. It also lists 3128 participants at risk for other adverse events and reports 7 other adverse events. These are the recorded figures; the registry does not provide a controlled comparison or a comparative risk estimate. Deaths are not reported in the registry record.

The listed top serious-event terms are tuberculosis pleuritis and pulmonary tumor, each recorded as 0.0%. Those entries should be read as the percentages reported in the record, not as evidence that the events were impossible or that risk was absent. The registry does not provide further detail in the information summarized for these terms, including an explanation of the displayed percentage values.

In general, adverse-event counts describe what was recorded during a study and do not by themselves establish that treatment caused an event. A single-arm observational study cannot directly compare event frequency with a control group, and the registry does not report comparative safety analyses. The figures also do not provide a complete account of event timing, severity beyond the serious-event distinction, or individual clinical circumstances. They should therefore be interpreted as descriptive registry entries, not as estimates of relative risk.

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

The record establishes that a completed, prospective, single-arm observational study enrolled 3130 participants and included 3128 in its analysis. It identifies repeated Klacid SR administration in routine clinical practice as the treatment context and describes a physician-assessed response endpoint during Day 8 - 16. It also records a set of secondary outcomes and basic adverse-event counts.

The record does not establish the frequency of primary endpoint response. The number of participants judged to have symptom disappearance or significant alleviation, the number without such a response, and a response proportion are not reported in the registry record. Without those outcome data, the magnitude and precision of the observed response cannot be assessed. No p-value or confidence interval for the primary outcome is reported either.

Even if a response estimate were available, the single-arm observational design would not by itself show that treatment caused the outcome. There is no concurrent comparator to distinguish treatment-associated outcomes from the natural course of illness or other aspects of routine care. The registry also does not report a detailed adjustment strategy that could address differences in participants or care.

The record does show that two enrolled participants were excluded from analysis because they were less than 18 years of age and did not meet entry criteria. It does not report the completeness of the primary outcome data among the analyzed participants or how any missing values were handled. This leaves uncertainty about the endpoint analysis population beyond the stated exclusions.

The safety entries are descriptive: 2 serious adverse events and 7 other adverse events are recorded among 3128 participants at risk. The record does not report deaths, and two serious-event terms are listed at 0.0%. These entries do not provide a comparison of safety against another treatment or no treatment. Taken together, the registry supports a description of the study’s question, design, population, and recorded safety counts, but not a quantified conclusion about primary effectiveness or comparative safety.

14. Why This Trial Matters Statistically

This study is statistically notable because it addresses repeated treatment in a routine-care setting rather than a randomized comparison. Observational studies can document how treatment and outcome assessment occur in clinical practice, across multiple sites and types of treating clinicians. That setting can make the data relevant to describing practice, while also creating interpretive limits: treatment selection and clinical assessment are not controlled through random assignment.

The primary endpoint reflects a clinician’s overall judgment of symptom disappearance or significant alleviation, supplemented by objective findings when available. Such an endpoint brings together patient symptoms and clinical observations, but it also raises measurement questions. Standardized assessment criteria, consistent availability of objective measures, and assessor procedures help readers judge how comparable outcome classifications are. Those details are not reported in the registry record.

The contrast between the enrolled population and the analysis population is also important. The registry explains the exclusion of two participants who were younger than 18 years, but does not describe other missing outcome information or its handling. A transparent account of exclusions, missingness, and analysis populations helps readers understand precisely which participants contribute to an estimate.

Most importantly, the posted registry information does not include the primary outcome result or a detailed statistical analysis. An endpoint definition can clarify what investigators intended to measure, but it cannot substitute for the observed count, estimate, and uncertainty. The listed 11 outcome measures make prespecification and multiplicity handling relevant statistical considerations, yet those methods are not reported.

The record therefore illustrates a central distinction in clinical statistics: a study can have a clearly stated clinical question and a substantial enrolled population while still offering limited information for estimating an effect if outcome results and analysis details are absent. Its observational design can describe outcomes in treated patients, but without a comparator it cannot provide a controlled treatment contrast. These features matter when judging what conclusions the available record can support.

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 central limitation is that the primary endpoint result is not reported in the registry record. Although the outcome definition and assessment period are stated, there is no response count, proportion, confidence interval, or p-value. The study’s primary effectiveness question therefore cannot be answered quantitatively from the recorded results.

The single-arm observational design has no concurrent control group. Outcomes after treatment cannot be separated from other explanations, such as the natural course of the respiratory condition or differences in routine clinical care. Allocation details are not stated, and no comparative analysis is reported. The registry does not provide information about adjustment for differences among participants or sites.

The endpoint depends on physician judgment of symptom disappearance or significant alleviation, with objective findings considered when available. The record does not report a standardized symptom scale, assessor training, procedures to ensure consistent judgments, or the extent to which objective information was available. This limits assessment of measurement consistency and comparability across participants and sites.

Although 3128 of 3130 enrolled participants were included in the analysis, the registry explains only the exclusion of two participants who were less than 18 years of age. Endpoint completeness, withdrawals, missing-data handling, and sensitivity analyses are not reported. A sample-size justification and detailed analysis plan are also not reported. The registry lists 11 outcome measures but zero analyses, leaving the analysis strategy and any multiplicity handling unclear.

Safety information is descriptive and lacks a concurrent comparator. The registry records serious and other adverse-event counts, but comparative safety estimates and deaths are not reported. The listed serious-event terms at 0.0% cannot be interpreted beyond their stated registry values without additional denominator and reporting context.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluation of Effectiveness of the Treatment After Repeated Administration of Klacid®SR — NCT01130883.
• Registry record last updated 2025-10-06; status last verified 2011-09.
• Results first posted 2011-08-23.
• 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

NCT01130883 is a completed, prospective, single-arm, multicenter observational study in the Czech Republic, sponsored by Abbott. It enrolled 3130 participants with respiratory infections, including acute tracheitis, acute tracheobronchitis, acute bronchitis, acute exacerbation of chronic bronchitis, or mild community-acquired pneumonia. The study examined repeated Klacid SR treatment in routine clinical practice among patients with prior treatment from 6 weeks to 24 months earlier.

The primary endpoint was physician-assessed symptom disappearance or significant alleviation, recorded as “yes” or “no” during Day 8 - 16. The analysis included 3128 participants; two were excluded because they were less than 18 years of age. The primary response result and detailed statistical analyses are not reported in the registry record. Safety entries include 2 serious adverse events and 7 other adverse events among 3128 participants at risk; deaths are not reported.