Retrospective Chart Review Study to Assess Characteristics, Treatment Outcomes and Resource Use of Adults Hospitalized for CAP and CSSTi Treated With Zinforo in Multiple Countries: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Retrospective Chart Review Study to Assess Characteristics, Treatment Outcomes and Resource Use of Adults Hospitalized for CAP and CSSTi Treated With Zinforo in Multiple Countries (NCT04198571), a registered phase not stated study. The primary outcome is Number of Participants With Clinical Response.

2. Clinical Question

The study concerns hospitalized adults treated for either of the two specified infections. The registry lists an enrollment of 317, but the clinical question is descriptive rather than a randomized comparison of treatments. The record describes a retrospective chart review across multiple countries in usual care. It does not identify the countries in the information recorded.

The primary question is about the number of participants meeting the relevant clinical-response definition from Day 1 of Zinforo treatment until the end of treatment. The observation period was up to a maximum of 35 days for CAP and up to a maximum of 60 days for cSSTI. The endpoint uses different clinical criteria for the two conditions, so a response in one group does not mean precisely the same measured event as a response in the other.

This design can describe outcomes among the people whose records met the study criteria. It cannot, by itself, establish what would have happened to comparable patients receiving another treatment or no Zinforo. The registry record does not report primary response counts or a causal comparison. It also does not report a statistical plan that would support interpreting the descriptive results as an estimate of treatment effect.

3. Trial Design

This is a completed, multinational retrospective chart review of adults hospitalized with CAP or cSSTI who were treated with Zinforo (ceftaroline fosamil) in usual care. The registry lists Pfizer as the sponsor, an enrollment of 317, a start date of 2020-05-17 and a primary completion date of 2021-07-23. The study description says the retrospective data were evaluated in approximately 14 months of the study.

Because the study looks back at clinical records rather than assigning treatment prospectively, the record describes treatment received in practice, not a randomized intervention. Allocation is not stated. The listed treatment arm includes adults treated with Zinforo for CAP or cSSTi, and the outcome information is organized by infection group. The CAP group has 185 participants at risk for the serious-event summary, and the cSSTI group has 132. These are safety-summary denominators and should not be assumed to define every analysis population.

The primary endpoint is a participant count for clinical response, assessed from the first day of Zinforo treatment to the end of treatment, with condition-specific maximum follow-up periods. The study also lists outcomes related to treatment outcomes and resource use, consistent with its stated objectives. The registry record lists 96 outcome measures and 0 analyses. The actual analysis methods, including whether models or adjustment for patient characteristics were used, are not reported in the registry record.

No randomized control arm or treatment allocation procedure is described. As a result, differences between CAP and cSSTI participants would reflect distinct infection populations and their clinical circumstances, not a treatment contrast. The record does not state a protocol-based sample-size justification, an interim-analysis plan or a prespecified statistical analysis plan. Its completion status is listed as completed, but that status alone does not indicate that every planned outcome is reported.

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

Analysis population for the primary outcome, as defined in the registry: Full analysis set included all participants with the respective type of infection who were eligible for the study and whose data was entered into the study database.

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: Full analysis set included all participants with the respective type of infection who were eligible for the study and whose data was entered into the study database.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Clinical Response, measured over Day 1 of Zinforo treatment till end of Zinforo treatment: up to maximum of 35 days for CAP; up to maximum of 60 days for cSSTI (from the retrospective data evaluated in approximately 14 months of the study).

The primary endpoint is the number of participants with clinical response during Zinforo treatment. The measurement begins on Day 1 of treatment and continues to the end of treatment, up to a maximum of 35 days for CAP and 60 days for cSSTI. It is a binary outcome at the participant level: a person either meets the relevant response definition or does not. The registry record does not report the response counts.

For CAP, clinical response requires both clinical stability and clinical improvement. Stability is defined using temperature, heart rate, respiratory rate, systolic blood pressure, oxygen saturation and the absence of recorded confusion or disorientation, according to the described IDSA criteria. Improvement requires improvement in at least 1 of 4 baseline symptoms—cough, dyspnea, pleuritic chest pain or sputum production—with worsening of none. The specified stability thresholds are temperature less than or equal to 37.8 degrees Celsius, heart rate less than or equal to 100 beats per minute, respiratory rate less than or equal to 24 breaths per minute, systolic blood pressure greater than or equal to 90 mmHg, and oxygen saturation greater than or equal to 90%.

For cSSTI, response requires at least a 20% reduction from baseline infection area and cessation of spread, measured by total infection area. These definitions operationalize clinical status in ways relevant to each infection. They are not interchangeable measures: the CAP definition combines stability and symptom change, while the cSSTI definition uses infection-area change and spread. Because the record gives no response counts, the endpoint definition can be described, but the observed frequency of response cannot be interpreted.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is the primary measure?

The primary endpoint is a count of participants meeting a response definition. In statistical terms, the underlying outcome for each participant is binary: response or no response. A count can be informative about how many people met the criterion, but it is most interpretable alongside a clearly defined population and denominator. The full-analysis-set description says it includes eligible participants with the respective infection whose data were entered into the study database. The primary response counts and corresponding denominators are not reported in the registry record, so no response proportion or uncertainty interval can be interpreted in the registry record recorded.

Although the endpoint is categorized as binary, the clinical event differs across conditions. CAP response requires stability and improvement in specified symptoms; cSSTI response uses change in infection area and cessation of spread. Combining the two conditions into a single unqualified response estimate would obscure that difference. Any analysis that combines them would need a stated rationale and method; neither is reported in the registry record.

What can a confidence interval tell a reader?

General statistical explanation: a confidence interval describes the range of values compatible with a data-based estimate under the assumptions of the chosen method. It communicates uncertainty from sampling and, depending on the method, other modeled sources of uncertainty. A narrow interval indicates greater statistical precision than a wide interval, but precision does not remove bias from selection, incomplete records or confounding. An interval around a treated-cohort response frequency would not, on its own, turn a retrospective description into a causal treatment comparison.

No confidence interval for the primary response outcome is reported in the registry record. The record also does not report a specific inferential test, regression model, adjustment set or method for constructing intervals. Accordingly, no claim about statistical significance or precision of the primary outcome can be made from these registry entries.

What does over-dispersion mean in general?

General statistical explanation: over-dispersion occurs when observed variability in count data exceeds what a simple model assumes. If a model underestimates variability, standard errors may be too small and intervals too narrow. A suitable analysis might use a model that allows extra variability, or another approach supported by the data structure. This is a general consideration for count outcomes, not a reported feature of this study. The registry record does not report a count model, a dispersion estimate or an over-dispersion adjustment.

The primary measure is described as a participant count with a binary interpretation, rather than as a repeated count of events per person. The safety figures also concern participants affected, as well as deaths, and should not be treated as recurrent-event rates without further definition. The record does not state whether events could be repeated for an individual or how such events were handled analytically.

How should the sample-size illustrations be understood?

The planning illustrations use the observed effect as a reference and consider the stated fraction of that effect to detect. The assumptions are a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. For time-to-event outcomes, the convention is a total number of events based on Schoenfeld; other outcomes are expressed as participants per arm. Such calculations describe hypothetical planning requirements under stated assumptions. They are not observed power and are not a record of the study’s original design.

This distinction matters because the study is a retrospective, treated-cohort review, while the illustration assumes two equally allocated arms. The registry record does not describe a randomized two-arm comparison. The exact effect fractions and calculated sample-size values are not reported in the registry record for this explanation. The registry also does not report a sample-size justification used to plan the chart review. Therefore the illustrations cannot establish that the review was adequately powered for its primary endpoint, nor can they repair the lack of a comparator.

More generally, a sample-size calculation depends on the outcome, target effect, error rate, allocation, analysis method and assumptions about the data. If those assumptions do not match the study design or the available records, the resulting planning quantity may not describe the precision of the actual study. A retrospective review may also be limited by which eligible records are available, rather than by a prospectively selected sample size.

Which analysis details are absent?

The record does not report which statistical tests or models were used, how baseline characteristics were summarized, whether any covariates were adjusted for, or how confidence intervals were constructed. It does not report an interim-analysis procedure, a hierarchy for outcomes or a multiplicity adjustment. Nor does it state how treatment duration, missing chart entries or differences among study countries were handled analytically. These are not details that can be inferred from the endpoint definitions or the study’s completed status.

General statistical explanation: an analysis plan helps distinguish prespecified questions from exploratory ones and clarifies how estimates, uncertainty and multiple outcomes will be handled. Without that information, readers should avoid attributing a particular statistical procedure or confirmatory status to an outcome. The record’s listing of 96 outcome measures and 0 analyses is registry metadata, not a substitute for a reported analysis plan or outcome-specific 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("Participants With CAP", "Participants With cSSTI")
n      <- c(185, 132)
events <- c(151, 118)
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  Participants With CAP  185  151  81.6  75.3  86.9  75.4  86.5  75.4  86.5
ARM  Participants With cSSTI  132  118  89.4  82.8  94.1  83.0  93.6  83.0  93.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 96 outcome measures and 0 analyses. It does not report how these measures were prioritized, whether a primary-to-secondary testing hierarchy was used, or whether any adjustment for multiple comparisons was planned or applied. When many outcomes are examined, the chance of finding an apparently unusual result can increase if each is interpreted independently. General statistical practice may address this through prespecified priorities or multiplicity procedures, but no such procedure is reported in the registry record.

The primary endpoint is identified as the number of participants with clinical response, with separate definitions for CAP and cSSTI. However, the response counts are not reported in the registry record. The registry record does not report whether outcomes were analyzed separately by infection type, combined, or adjusted for participant characteristics. It also does not state whether the 96 listed measures represent distinct analyses, overlapping measures or different time points; the count alone does not resolve those questions.

The full-analysis-set description includes eligible participants with the relevant infection whose data were entered into the study database. The record does not report how many eligible records lacked required information, whether any participants were excluded from a particular outcome analysis, or how missing clinical assessments were handled. It does not state whether missingness was considered likely to be related to participants’ condition or care. Those details matter because complete-record analyses can be biased if the availability of chart information is related to outcome.

The registry does not report an imputation method, a sensitivity analysis for missing data, or rules for handling incomplete symptom or infection-area documentation. It also does not explain how the full analysis set was applied to each outcome. Without those details, the extent and direction of missing-data bias cannot be assessed. The completed status does not establish that missingness was absent or that all listed outcomes were analyzed.

12. Safety Results

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

Deaths

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

Serious events with the highest arm-level rate: agranulocytosis (0.8%), drug hypersensitivity (0.8%).

The safety summary separates participants with CAP from participants with cSSTI. It lists 0 serious adverse events affecting participants with CAP and 2 affecting participants with cSSTI. The listed at-risk counts are 185 for CAP and 132 for cSSTI. Those counts provide context for the reported summaries, but they do not support a comparison with another treatment because the registry record does not include a control arm.

The record lists agranulocytosis at 0.8% and drug hypersensitivity at 0.8% among the top serious adverse-event terms. These are reported percentages, not comparative estimates. The record does not provide further detail about the event circumstances, timing, recurrence, or causal attribution. The terms should not be interpreted as proof that treatment caused the events.

Deaths are listed as 31 for participants with CAP and 15 for participants with cSSTI. These are counts in the registry safety information; they do not establish why deaths occurred or whether they were related to treatment. The registry entries recorded do not specify the deaths’ causes or their relationship to serious adverse events. Nor do they provide a comparative risk estimate or uncertainty interval. In a retrospective treated cohort, safety counts describe recorded events in the studied groups and require clinical and study-context details for further interpretation.

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

The study’s value lies in describing characteristics, treatment outcomes and resource use among adults hospitalized with CAP or cSSTI who received Zinforo in usual care. A retrospective chart review can capture care as documented in clinical practice and can characterize the population and recorded outcomes. In this record, the endpoint definitions and safety summaries provide some context for what was assessed.

However, the primary clinical-response counts are not reported in the registry record. Therefore, the response frequency and its precision cannot be stated. The record’s enrollment figure of 317 does not supply the missing endpoint result, and it should not be substituted for a response denominator. The safety entries likewise do not establish comparative risks or treatment causation.

The design does not describe random allocation or a like-for-like control group. Outcomes among people who received Zinforo may reflect their underlying illness, treatment selection, other care and documentation in their charts. Without a suitable comparison and reported methods to address these differences, the study cannot isolate a treatment effect. Comparing the CAP and cSSTI groups would not solve that problem because they have different infections and different response definitions.

The record also does not report the statistical analysis methods, missing-data handling or multiplicity approach. Those omissions limit assessment of precision and robustness, especially given the number of outcome measures listed. A completed registry status indicates the study is marked completed, not that every result or analysis needed for independent interpretation is available.

Accordingly, the appropriate interpretation is bounded: this is a retrospective description of treated adults, with condition-specific definitions and selected safety counts. It does not provide a reported primary response estimate, a randomized treatment comparison, or evidence that observed deaths or adverse events were caused by Zinforo. It also cannot answer how outcomes would differ under another treatment based on the record information.

14. Why This Trial Matters Statistically

This study is statistically important as an example of how real-world chart reviews answer descriptive questions while leaving causal questions unresolved. The registry concerns adults hospitalized with two clinically different infections, treated in usual care. Such records may help characterize who received treatment and what outcomes were documented, but the design is not equivalent to a randomized comparison.

The primary endpoint illustrates why operational definitions matter. CAP response depends on clinical stability and change in symptoms, while cSSTI response depends on infection-area reduction and cessation of spread. These definitions make the outcome interpretable within each clinical setting, but they also mean that a shared label of clinical response should not be taken to imply a directly comparable event across both groups.

The registry record also illustrates the difference between naming an outcome and reporting its result. It specifies the response criteria and the observation windows, yet the primary response counts are not reported in the registry record. Statistical interpretation depends on both a clear endpoint and the data needed to estimate it, including the analysis population and denominator. The enrollment figure alone cannot supply that information.

Finally, the record lists many outcome measures but does not report an analysis plan, missing-data procedures or multiplicity handling. These details help readers distinguish confirmatory findings from exploratory descriptions and judge how stable estimates might be. Their absence does not mean that no analysis occurred; it means the methods are not reported in the registry record. Careful interpretation therefore separates the useful descriptive scope of the review from conclusions about treatment effects that the design and reported results do not 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 study is retrospective and relies on information recorded during usual care. Clinical measurements, symptoms and infection-area assessments may not have been collected uniformly for research purposes. The registry record does not report procedures for checking chart completeness, standardizing measurements across countries or resolving conflicting entries. Missing or inconsistently documented information could affect which participants contribute to an outcome and whether they meet its definition.

There is no randomized comparator described, and allocation is not stated. Treatment selection may be related to patient condition or clinical circumstances, so outcomes in the treated cohort cannot be separated from those factors using the information reported. The CAP and cSSTI groups are not substitutes for each other as controls: their infections, response criteria and maximum observation periods differ.

The primary clinical-response counts are not reported. This prevents interpretation of the principal endpoint’s observed frequency and precision. Although the record lists 96 outcome measures, it lists 0 analyses and does not report which outcomes were analyzed, the statistical methods, covariate adjustment, interval estimation or multiplicity procedures. The approach to missing data and analysis populations for individual outcomes is also not reported.

The safety entries provide counts and selected terms, but the registry entries recorded do not give causal attribution, detailed event timing or the circumstances of deaths. The registry record does not identify the participating countries in the information, so geographic variation cannot be evaluated. It also does not report a protocol-based sample-size justification or an interim-analysis plan. These limitations constrain both reproducibility and the strength of conclusions that can be drawn from the record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Retrospective Chart Review Study to Assess Characteristics, Treatment Outcomes and Resource Use of Adults Hospitalized for CAP and CSSTi Treated With Zinforo in Multiple Countries — NCT04198571.
• Registry record last updated 2024-03-26; status last verified 2023-09.
• Results first posted 2024-03-26.
• 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

NCT04198571 is a completed multinational retrospective chart review of adults hospitalized with CAP or cSSTI and treated with Zinforo (ceftaroline fosamil) in usual care. The registry lists Pfizer as sponsor, enrollment of 317, a start date of 2020-05-17 and primary completion on 2021-07-23.

The primary outcome is the number of participants with clinical response, using different criteria for CAP and cSSTI and follow-up from Day 1 of treatment to its end, up to the specified condition-specific maximum. The primary response counts are not reported in the registry record. Safety information lists serious adverse events and deaths separately by infection group, without a treatment comparator or causal attribution. The record lists 96 outcome measures and 0 analyses; statistical methods, missing-data handling and multiplicity procedures are not reported.