Real-World Observational Study Of Zavicefta to Characterize Use Patterns: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Real-World Observational Study Of Zavicefta to Characterize Use Patterns (NCT03923426), a registered phase not stated study. The primary outcome is Number of Participants Who Received at Least One Dose of Ceftazidime-Avibactam Classified According to Type of Usage as Monotherapy or Combination Therapy: FAS 72+ Population.

2. Clinical Question

This is primarily a description of use patterns, not a randomized test of whether ceftazidime-avibactam is better than another treatment. The registry’s broader objective also includes describing effectiveness and safety in routine practice. However, the designated primary outcome is the number of participants classified by type of use. The primary outcome counts are not reported in the registry record, so the size of the monotherapy and combination-therapy groups cannot be described from this record.

The study concerns treatment decisions made in ordinary care rather than treatment assigned by a study protocol. The registry describes eligible adults treated at participating sites from the relevant country-specific availability dates. As treatment was at physician discretion, the clinical circumstances and reasons for choosing monotherapy or combination therapy may vary. The record does not specify those reasons or provide a randomized comparison that could separate treatment effects from differences between patients or care settings.

3. Trial Design

NCT03923426 is a completed, non-interventional medical chart review study sponsored by Pfizer. The registry lists enrollment of 572 and study dates from 2018-11-27 to primary completion on 2022-03-28. Its official title identifies the study as EZTEAM and describes its aim as characterizing use patterns, effectiveness, and safety for ceftazidime-avibactam in routine practice.

The brief summary describes adults treated at participating sites in approximately 12 countries, with possible expansion as the treatment became available in additional countries. Eligibility was based on treatment in routine practice from 01 January, 2018 onwards, or from the date of launch in a country if that was later. The registry does not report the final country list or the number of sites contributing data.

Because this was observational, physicians made treatment decisions according to standard care. The registry says no study drugs were posted. It does not describe randomized allocation; the record’s comparison note cautions that treatment groups are not a like-for-like control comparison. Consequently, differences between observed treatment groups, if examined, would not by themselves establish that treatment choice caused an outcome.

The primary outcome classifies participants receiving at least one dose as having received monotherapy or combination therapy. The defined analysis population is FAS 72+, meaning participants with at least 72 hours of exposure to ceftazidime-avibactam. The outcome timeframe runs from the start to the end of index treatment, with a maximum of 179 days of treatment exposure. The record describes data evaluated in approximately 40 months of the study. It lists 35 outcome measures and zero analyses, but does not report the primary outcome counts or a statistical analysis plan.

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: Data was abstracted from medical records and evaluated over approximately 40 months of this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: FAS72+ population included all participants with at least 72 hours of exposure to ceftazidime-avibactam.

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: The full analysis set (FAS) included all those enrolled participants who met the study eligibility criteria. Baseline characteristics were analyzed and reported for FAS72+ which included FAS participants with at least 72 hours of exposure to ceftazidime-avibactam and FAS72- which included FAS participants with less than (\<) 72 hours of exposure to ceftazidime-avibactam.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Received at Least One Dose of Ceftazidime-Avibactam Classified According to Type of Usage as Monotherapy or Combination Therapy: FAS 72+ Population, measured over From start of index treatment to end of index treatment (maximum 179 days of treatment exposure) (from the data evaluated in approximately 40 months of the study).

The primary endpoint is a count of participants who received at least one dose of ceftazidime-avibactam, classified according to whether it was used as monotherapy or in combination with other therapy. The index date is the start date of ceftazidime-avibactam. The endpoint applies to the FAS 72+ population, defined as participants with at least 72 hours of exposure, and covers index treatment up to a maximum of 179 days.

This endpoint is useful for describing how the treatment was used in routine practice. Separating monotherapy from combination therapy captures an important feature of treatment patterns without requiring an assigned treatment group. A count can indicate the size of each usage category when those counts are available. It does not, on its own, measure clinical benefit, compare treatment effectiveness, or show why physicians selected a particular approach.

The registry record does not report the primary endpoint counts. It therefore does not establish how many participants were classified in either category, nor does it provide an estimate of uncertainty around those counts. The primary endpoint’s count-based description should also be distinguished from the study’s broader stated aims concerning effectiveness and safety; those aims do not substitute for reported endpoint results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a count endpoint tell the reader?

The primary measure is a count of participants classified by type of use. Counts are descriptive: they state how many participants fall into a category, rather than estimating a treatment effect against a control group. In general, a count is most interpretable when its population, event or category definition, and observation period are clear. The registry defines the primary population as FAS 72+, specifies at least 72 hours of exposure, and identifies the index treatment period as the timeframe.

The record does not provide the category counts. Consequently, the reader cannot assess the relative frequency of monotherapy and combination therapy, the precision of either count, or whether categories account for all participants eligible for the endpoint. No proportion or comparison should be inferred without the underlying counts and denominators.

Why does the observational design matter?

In a randomized trial, treatment assignment is intended to create groups that are comparable in expectation. This study instead reviewed treatment given in routine practice, with the physician choosing care. Such data can describe what happened in participating settings, but treatment groups may differ before treatment begins. For example, clinical condition or prescribing context may influence both treatment choice and later outcomes. These are general concerns about observational comparisons; the registry does not report whether or how they were measured or adjusted for in this study.

The registry’s comparison note says the arms are not a like-for-like control comparison, and allocation is not stated. The record therefore does not support treating any apparent difference between treatment groups as a causal effect. It also does not report an adjusted effect estimate or details of a statistical model.

How should the analysis population be read?

The primary outcome is defined for FAS 72+, which includes participants with at least 72 hours of exposure to ceftazidime-avibactam. This is an exposure-defined analysis population. In general, restricting an analysis by observed treatment exposure can make the population different from everyone who started treatment: exposure duration may be related to clinical course, treatment decisions, or data availability. This is a methodological consideration, not a claim about what happened to participants in this study. The record does not describe the reasons for the threshold or how participants with less exposure were handled in other outcomes.

The adverse-event record uses 569 participants at risk as its denominator, while enrollment is 572. It does not explain how these populations relate to FAS 72+ or why the risk count differs from enrollment. Readers should preserve the stated denominators rather than treating them as interchangeable.

What do uncertainty measures mean?

In general, a confidence interval describes a range of values compatible with the data and the method used to calculate it. Its width reflects statistical precision: a wider interval indicates more uncertainty about the estimate than a narrower interval, all else equal. A confidence interval does not repair bias from non-random treatment selection, incomplete recording, or a poorly defined comparison. The registry record does not report confidence intervals for the primary endpoint or an adjusted treatment-effect estimate.

In general, p-values assess how compatible data are with a specified statistical null model, under the assumptions of the analysis. They do not measure the probability that a treatment works, and they do not establish causation. The registry record lists zero analyses and does not report a primary-outcome p-value or describe the testing procedure. No inferential conclusion should be attributed to an unreported analysis.

How should planning calculations be interpreted?

The sample-size assumptions describe planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The intended effect is defined as a stated fraction of the observed effect. For time-to-event calculations, the assumption describes a total event count; other planning calculations are expressed as participants per arm. These illustrations are not the study’s own design justification and are not observed power. The registry record does not report its sample-size justification or establish that the observational study was designed around those calculations.

In general, a planning calculation asks how much information might be needed under a chosen effect and set of assumptions. It is not a measure of the probability that a completed study has detected a true effect. Since this study is observational and the record does not report a randomized comparison, planning values based on two arms should not be read as evidence that the study had a valid causal contrast.

Why can over-dispersion matter?

In general, over-dispersion occurs when observed variability in count data is greater than a model assumes. If ignored, standard errors can be too small and confidence intervals too narrow, making results appear more precise than they are. Appropriate handling depends on the outcome and model. The primary outcome is described as participant counts, but the registry record does not report a fitted count model, dispersion estimate, or any adjustment for over-dispersion. This general issue should not be mistaken for a method known to have been used in this study.

More broadly, interpretation depends on outcome definitions, analysis populations, missing-data handling, and the statistical plan. Several of these details are not reported in the registry record. The record’s stated design and outcome definitions can be described, but the omitted analysis information prevents a full assessment of how estimates were produced.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 35 outcome measures and zero analyses. It does not report a statistical analysis plan describing which outcomes were confirmatory, how outcomes were prioritized, or whether any adjustment for multiple testing was planned or performed. The primary outcome is identified by title, but the record does not provide its result or a complete inferential analysis.

In general, testing many hypotheses can increase the chance of obtaining at least one apparently noteworthy result by chance. Methods for addressing multiplicity depend on the purpose and structure of the analyses. Without a reported plan and results, it is not possible to determine how multiplicity was handled in this study. The existence of multiple registered outcomes alone does not show that a particular adjustment was needed or applied.

The registry record does not describe missing-data rates, reasons for missingness, imputation, or sensitivity analyses. Missing information can affect both descriptive summaries and comparisons, especially when its occurrence is related to participant characteristics or outcomes. This is a general concern; the record does not establish whether, or to what extent, missing data affected the study.

The primary analysis population is FAS 72+, defined by at least 72 hours of treatment exposure. The record does not explain how this population was determined for every outcome, how participants outside it were handled, or whether other analysis populations were used. The adverse-event denominator is reported as 569 at risk, while enrollment is 572; the registry does not explain the difference or its relationship to the primary population. These omissions limit the ability to assess selection, completeness, and consistency across outcomes.

11. 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

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: multiple organ dysfunction syndrome (0.2%), cholestasis (0.2%), hepatocellular injury (0.2%), clostridium difficile colitis (0.2%), altered state of consciousness (0.2%).

The registry lists 569 participants at risk for serious adverse events and reports five affected participants. For other adverse events, it also lists 569 at risk and reports two affected participants. Separately, it reports 170 deaths. These are the posted descriptive figures; the record does not provide enough information to determine the timing, causes, or relationship of deaths to treatment.

The most frequently listed serious-event terms are multiple organ dysfunction syndrome, cholestasis, hepatocellular injury, Clostridium difficile colitis, altered state of consciousness, and neurotoxicity. Each term is accompanied by a reported value of 0.2%. The registry record does not explain the term-level denominator or whether participants could contribute more than one event term. These percentages should therefore be read as reported term-level values, not converted into participant counts or treated as a complete account of safety.

In general, adverse events observed during treatment do not by themselves show that treatment caused them. A causal assessment requires context about the underlying illness, event timing, alternative explanations, and a suitable comparison. This observational study does not provide a randomized control group in the registry record. The safety counts should be understood as descriptive reports from the study, not as a causal comparison or medical advice.

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

The primary outcome was designed to describe how ceftazidime-avibactam was used: as monotherapy or as combination therapy among participants with at least 72 hours of exposure. That is a useful question for understanding routine practice. However, the primary outcome counts are not reported in the registry record, so the intended description cannot be recovered from the posted result information.

The record does show that the study was non-interventional, completed, and based on medical chart review. It also reports the enrollment, study dates, an exposure-defined primary population, and descriptive safety figures. Those details characterize the study and its reporting, but they do not establish that treatment caused an outcome or that it was more or less effective than another approach.

In general, observational studies can provide evidence about treatment use and outcomes in clinical settings. Their interpretation depends on who was included, how outcomes were recorded, how missing information was handled, and whether differences between treatment groups were addressed. The registry record does not report enough analysis detail to evaluate those issues fully. Its note that the groups are not like-for-like controls is particularly important when considering any comparative interpretation.

The reported adverse-event counts and term-level percentages are descriptive, and the record does not establish causal attribution. The deaths figure likewise cannot be interpreted as a treatment effect without further context and an appropriate comparison. The record also does not report the primary outcome estimates, uncertainty intervals, or the analysis plan. Accordingly, it supports a cautious account of the study’s design and the reported safety figures, but not a conclusion that ceftazidime-avibactam does or does not work.

13. Why This Trial Matters Statistically

Real-world treatment patterns are shaped by decisions made in routine care, and those decisions can differ across patients and settings. A chart review can document how a treatment was used outside a randomized assignment process. That makes the study’s stated focus on monotherapy and combination therapy relevant to understanding prescribing practice, provided the classification counts and population details are available.

The statistical distinction between describing use and estimating effectiveness is central. A count of treatment categories can describe practice, but it does not provide a fair treatment comparison by itself. For comparative effectiveness, differences in patient circumstances and clinical decisions may influence both treatment choice and outcomes. The registry itself cautions that the groups are not like-for-like controls, so a comparison should not be interpreted as a causal estimate without a justified analysis.

The record also illustrates why outcome definitions and analysis populations matter. The primary outcome is restricted to FAS 72+, while safety information uses a stated at-risk denominator that the registry does not reconcile with enrollment. Readers need those definitions to understand who contributes to each result and what the resulting counts mean.

Finally, a completed study status and a substantial registry record do not guarantee that all results or statistical methods are reported. Here, the primary outcome counts, multiplicity approach, missing-data handling, and analysis plan are not reported in the registry record. Recognizing these gaps is part of statistical interpretation: it keeps the distinction clear between what the study set out to describe, what the registry reports, and what remains uncertain.

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 primary limitation for interpreting the main question is that the registry record does not report the monotherapy and combination-therapy counts. It therefore does not permit a direct description of the primary outcome, despite defining its population and timeframe.

The observational design means treatment was selected in routine practice at physician discretion. The registry cautions that treatment groups are not like-for-like controls, and allocation is not stated. It does not report whether confounding factors were measured or adjusted for, so comparative effectiveness cannot be assessed from the record. The registry also does not provide an analysis plan, effect estimates, confidence intervals, or primary-outcome tests.

The primary population requires at least 72 hours of exposure, which makes it an exposure-defined group rather than an unrestricted description of everyone enrolled. The record does not explain the rationale for this threshold or how those with shorter exposure were handled. It reports 572 for enrollment and 569 at risk in the adverse-event group, without explaining the relationship between those figures.

Other trial-specific information is also absent: the final participating-country and site counts, the handling of missing chart data, the multiplicity approach across the 35 outcome measures, and the reasons for treatment choices are not reported in the registry record. The safety information is descriptive and does not include a randomized control group. These limitations constrain conclusions about representativeness, precision, bias, and causal effects.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Real-World Observational Study Of Zavicefta to Characterize Use Patterns — NCT03923426.
• Registry record last updated 2024-06-21; status last verified 2024-01.
• Results first posted 2023-12-18.
• 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.

18. Record Summary

NCT03923426 is a completed, non-interventional medical chart review sponsored by Pfizer, with enrollment listed as 572. The record gives a study start of 2018-11-27 and primary completion on 2022-03-28. It describes routine-practice use of ceftazidime-avibactam in adults and identifies the primary outcome as the number of participants using it as monotherapy or combination therapy in the FAS 72+ population.

The primary outcome counts are not reported in the registry record. The adverse-event information lists 569 at risk, five participants affected by serious adverse events, two affected by other adverse events, and 170 deaths. The record lists 35 outcome measures and zero analyses. Its observational design and stated lack of like-for-like control groups limit causal comparisons; analysis details, missing-data methods, and multiplicity handling are not reported.