Pharmacokinetic/Pharmacodynamic Study of Doripenem in Febrile Neutropenic Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pharmacokinetic/Pharmacodynamic Study of Doripenem in Febrile Neutropenic Patients (NCT01401010), a randomized phase 4 study. The primary outcome is Mean (SD) Doripenem Pharmacokinetic Volume of Distribution Parameter in Febrile Neutropenic Patients.

2. Clinical Question

3. Trial Design

The registry describes NCT01401010 as a phase 4 study with randomized allocation, no masking, and a single-group model. Its title identifies a pharmacokinetic/pharmacodynamic study of doripenem in febrile neutropenic patients with possible bacterial infection. Enrollment is listed as 12, and the record status is completed. The record lists a start of 2010-08 and primary completion of 2012-02.

Doripenem 500 mg and Doripenem 1000 mg are the two dose groups in the posted primary outcome results. The same results also give a combined summary for both doses. Although allocation is labeled randomized, the registry model is labeled single group; the record does not explain this combination of design labels or provide details of the randomization procedure. It also does not identify a control treatment. The data therefore need to be read as reported dose-group descriptions, rather than as a clearly specified controlled comparison.

The primary outcome is a continuous pharmacokinetic measure reported as a mean and standard deviation in liters. The endpoint description says blood was obtained at 1, 4, 6, and 8 hours after at least two doses, and that levels were measured by HPLC assay. The endpoint timeframe is stated as 1, 4, 6, and 8 hours after at least two doses of drug. The registry lists a secondary aim involving Monte Carlo simulations against various Gram-negative isolates and probability of target attainment for 40% time above the minimum inhibitory concentration. Numerical results for that secondary aim are not reported in the registry record.

The registry does not report the study protocol, the rationale for the enrollment target, or details of masking beyond the designation of none. The primary outcome results include 5 participants for 500 mg, 6 for 1000 mg, and 11 in the combined summary; the record does not account for the difference between those endpoint counts and the enrollment of 12.

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: Each subject received drug and had serum samples drawn at 1, 4, 6, 8 hours after dosing.

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 Mean (SD) Doripenem Pharmacokinetic Volume of Distribution Parameter in Febrile Neutropenic Patients, measured over 1, 4, 6, 8 hours after at least two doses of drug.

The primary endpoint is the mean doripenem pharmacokinetic volume of distribution parameter in febrile neutropenic patients, reported in liters with a standard deviation. The endpoint description specifies patients with pneumonia and says serum samples were collected at 1, 4, 6, and 8 hours after at least two doses. Serum levels, described in mg/L, were measured using an HPLC assay. The listed outcome timeframe is the same set of post-dose sampling times.

Pharmacokinetic measures describe how a drug behaves in the body. In general, volume of distribution is a parameter relating the amount of drug in the body to its concentration in blood or plasma. It is used to characterize distribution, rather than directly measuring whether a treatment improves a clinical outcome. The registry does not give further details of the parameter’s calculation or an interpretive threshold for the reported values.

The outcome is summarized separately for the 500 mg and 1000 mg groups and for their combined results. Those summaries describe the observed values in the participants included in each group. They are not estimates of clinical effectiveness, and the means alone do not show how individual measurements varied; the standard deviations provide a description of that spread. The registry does not report confidence intervals for these means or an inferential test of a difference between dose groups.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a continuous measure, summarized by a mean and standard deviation. In general, a mean is the arithmetic average of the recorded measurements, while a standard deviation describes how dispersed those measurements are around that average. These are different kinds of information: the mean describes the group’s central value, and the standard deviation describes variability between observed measurements. A standard deviation does not by itself indicate how precisely the population mean has been estimated.

What can the group summaries tell the reader?

The reported values allow a descriptive account of the volume of distribution parameter in each dose group and in the combined group. They do not supply a formal comparison. The registry does not report a confidence interval, standard error, p-value, or model-based estimate for a difference between the two dose groups. A numerical contrast between the reported means should not be presented as a trial finding when the registry does not report that comparison. The record itself notes that values are missing or not estimable for a two-arm comparison of this continuous endpoint.

In general, a confidence interval gives a range of values compatible with the data under the assumptions of a statistical procedure. It helps communicate uncertainty in an estimate, but it does not guarantee that the true value lies in that range. No confidence interval for the primary endpoint means the registry entry does not provide that interval-based description of precision. The reported standard deviations still describe observed spread, but they cannot substitute for confidence intervals around the group means.

Why does the study label matter?

The registry labels allocation randomized, masking none, and model single group, yet the results include two doripenem dose groups. Design labels describe different features of a study, and they do not by themselves establish what comparison was planned or analyzed. The registry record does not explain the relationship between these labels, the assignment process, or the analysis plan. Without those details and without reported comparative estimates, the two group summaries should be interpreted descriptively rather than as a test of dose differences.

The listed sample-size assumptions describe a planning illustration using a two-sided significance level of 0.05, equal allocation, a normal approximation, and a specified fraction of an observed effect. Such illustrations are planning exercises, not observed power and not evidence that the trial was designed or sized according to those assumptions. The record does not report the trial’s own sample-size justification. In addition, the registry does not report an estimable two-group effect for this endpoint, so a planning illustration should not be mistaken for an observed comparison or a trial result.

How should Monte Carlo target attainment be understood?

In general, a Monte Carlo simulation repeatedly draws values from specified distributions to examine the behavior of a model under uncertainty. Probability of target attainment is a model-based quantity: it describes how often a defined pharmacokinetic target is reached under the assumptions and inputs used. The registry states that simulations were tested against various Gram-negative isolates and that the target was 40% time above MIC. The underlying simulation inputs, isolate-specific estimates, uncertainty, and numerical probabilities are not reported in the registry record. The simulation objective should therefore be distinguished from the observed primary pharmacokinetic summaries, and no target-attainment value can be inferred from those summaries alone.

In general, over-dispersion means that observed variability is greater than a statistical model assumes. When present, ignoring it can make uncertainty estimates too narrow. The registry does not report a model for the primary outcome or information that permits assessment of over-dispersion; this concept is relevant only as a general consideration, not as a finding about this study. The reported standard deviations are descriptive and do not establish whether a particular model assumption was met.

There are no posted analyses listed for the primary outcome. Consequently, the available record supports a limited statistical reading: identify the means, standard deviations, and group counts; distinguish those summaries from inferential results; and avoid claiming precision or comparative evidence that is not reported. The record does not describe adjustment for covariates or provide methods for handling repeated post-dose measurements, so no such methods should be assumed.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Doripenem 500 mg", "Doripenem 1000 mg", "Combined Results for Both 500 and 1000 mg")
n   <- c(5, 6, 11)
m   <- c(36.7, 49.9, 43.9)
sp  <- c(15.9, 18.1, 17.7)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Doripenem 500 mg  5  36.700  15.900  16.958  56.442
CARM  Doripenem 1000 mg  6  49.900  18.100  30.905  68.895
CARM  Combined Results for Both 500 and 1000 mg  11  43.900  17.700  32.009  55.791

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one secondary outcome concerning Monte Carlo simulations and probability of target attainment for 40% time above MIC. It does not report numerical results for that outcome, isolate-specific estimates, or a multiplicity procedure. The registry record also does not report how many statistical hypotheses were planned, whether any adjustment for multiple testing was used, or whether the secondary outcome was considered exploratory. Without those details, the impact of multiplicity on interpretation cannot be assessed.

For the primary endpoint, the record reports group means and standard deviations, but no comparative analysis. It does not report a missing-data method, an imputation procedure, or an analysis population definition. The enrollment is 12, whereas the primary outcome summaries include 5 participants for Doripenem 500 mg and 6 for Doripenem 1000 mg, with 11 in the combined result. The reason for this difference is not reported in the registry record. It should not be assumed that the unrepresented participant had missing measurements or was excluded for a particular reason.

The endpoint description says each subject received drug and had serum samples drawn at the specified times, but does not state whether all planned samples were obtained for every participant. The record does not explain how incomplete sampling, if any, was handled or whether the reported parameter could be calculated when some measurements were unavailable. It also does not describe an intention-to-treat, per-protocol, or pharmacokinetic analysis population. These omissions limit assessment of how the posted summaries relate to all enrolled participants.

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 5% reporting threshold.

The posted safety figures list 5 participants at risk in the Doripenem 500 mg group and 6 in the Doripenem 1000 mg group. For both groups, the registry reports zero participants affected by serious adverse events and zero affected by other adverse events. These are event summaries for the groups and counts shown; they do not establish that no events occurred outside the definitions or reporting captured in the registry.

The death counts are not reported in the registry record. No serious adverse-event terms are listed. The record does not give a safety observation period, detailed event descriptions, severity grading, or information about withdrawals due to adverse events. Those details cannot be inferred from the zero counts.

In general, an observed zero count is not proof that an event is impossible or that risk is absent. The safety figures should be read in light of the small reported group counts and the limited information in the registry entry. They do not support a broad safety conclusion or comparison between doses.

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

The results describe a pharmacokinetic parameter in participants listed in two doripenem dose groups and in a combined group. The reported means and standard deviations provide a snapshot of the recorded volume of distribution values, with group counts stated alongside them. They are useful as descriptive information about this study’s endpoint, but the registry does not provide confidence intervals or a formal dose comparison to quantify uncertainty around a difference.

The findings do not establish that one dose produces a different volume of distribution from the other. Although the registry lists randomized allocation, it also identifies the study model as single group and does not explain the design labels or report comparative analysis. The mean summaries alone cannot resolve those uncertainties. They also do not show whether a pharmacokinetic difference, if present, would affect bacterial outcomes or any clinical endpoint.

The stated secondary objective concerns simulated probability of attaining a 40% time-above-MIC target across various Gram-negative isolates. Numerical results for that objective are not reported in the registry record. The primary endpoint values cannot be used to reconstruct those simulations because their inputs and results are not given.

The record reports enrollment of 12 but endpoint summaries for 11 participants. It does not explain that difference, define the analysis population, or describe missing-data handling. These details matter when judging how representative the posted summaries are of the full enrolled group. The reported safety counts are also limited to the listed participants and do not include reported death counts or detailed event descriptions.

In short, the registry supports a description of the posted pharmacokinetic summaries and the limited safety counts. It does not support conclusions about comparative dose effects, clinical efficacy, target attainment, or the absence of safety risks. The strength of any interpretation is constrained by the small reported endpoint groups and the lack of inferential and analysis details.

14. Why This Trial Matters Statistically

This study is statistically relevant because it illustrates the distinction between describing pharmacokinetic data and testing a comparative hypothesis. Means and standard deviations communicate central tendency and observed variability, but they do not by themselves answer whether two dose groups differ. A reader needs an estimate of the comparison and its uncertainty to make that inferential distinction; neither is reported for the primary endpoint.

The record also shows why design labels should be read alongside the results. It identifies randomized allocation, no masking, and a single-group model, while listing two dose groups in the endpoint results. Those descriptions are not reconciled in the registry entry. Reporting the discrepancy transparently is important because design interpretation affects what comparisons are justified.

The endpoint counts also warrant attention. Enrollment is listed as 12, while the combined primary result includes 11 participants. The record does not explain this difference. Clear reporting of analysis populations and missing measurements helps readers assess the scope of a result and whether the analyzed participants correspond to those enrolled.

Finally, the secondary simulation objective and primary measured endpoint are distinct kinds of evidence. Simulation-based target-attainment estimates depend on modeling assumptions and input data, while the primary results summarize measured pharmacokinetic parameters. The record gives the objective but not the numerical simulation results. Keeping these evidence types separate prevents a stated analysis aim from being mistaken for a reported finding.

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 registry entry does not provide a protocol, detailed statistical analysis plan, or sample-size justification. It does not explain the combination of randomized allocation and a single-group model designation, or describe the method of assignment to the listed doses. This limits reconstruction of the intended design and comparison.

The primary outcome results are descriptive, with no reported confidence intervals, hypothesis test, or adjusted comparison between doses. The record states that values are missing or not estimable for a two-arm comparison of this continuous endpoint. It also does not describe the analysis population, handling of incomplete samples, or whether all scheduled post-dose measurements were available for each participant.

The reported endpoint counts do not match the stated enrollment: 5 participants are listed for Doripenem 500 mg, 6 for Doripenem 1000 mg, and 11 in the combined result, against enrollment of 12. The registry does not explain the difference. The outcome description specifies patients with pneumonia, while the listed condition is febrile neutropenia; the record does not further characterize the endpoint population.

Details needed to interpret the pharmacokinetic parameter, including its calculation method and any clinically meaningful threshold, are not reported in the registry record. The secondary simulation objective has no numerical results or input details. Safety reporting is limited to the listed affected counts; death counts and a safety observation period are not reported. These limitations constrain both statistical and clinical interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pharmacokinetic/Pharmacodynamic Study of Doripenem in Febrile Neutropenic Patients — NCT01401010.
• Registry record last updated 2015-10-14; status last verified 2015-10.
• Results first posted 2012-06-05.
• 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

NCT01401010 is a completed phase 4 doripenem pharmacokinetic/pharmacodynamic study in febrile neutropenic patients with possible bacterial infection. The registry lists randomized allocation, no masking, a single-group model, and enrollment of 12. The primary endpoint is the mean and standard deviation of a volume of distribution parameter in liters, with sampling described at 1, 4, 6, and 8 hours after at least two doses.

Primary results are reported for Doripenem 500 mg, Doripenem 1000 mg, and a combined group. The registry does not report an estimable two-dose comparison, confidence intervals, or inferential tests. The secondary objective concerns simulated probability of target attainment for 40% time above MIC, but numerical results are not reported in the registry record. Safety counts report zero serious and zero other adverse events in the listed groups; death counts are not reported. The difference between enrollment and the combined endpoint count is unexplained.