Effect of, OAT3, on the Renal Secretion of Cefotaxime: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of, OAT3, on the Renal Secretion of Cefotaxime (NCT00187655), a na phase 1 study. The primary outcome is Effect of OAT3 on Renal Secretion of Cefotaxime IV Based on Genotype.

2. Clinical Question

The study’s stated aim is to examine the role of the organic anion transporter OAT3 in renal secretion of cefotaxime. Its genotype-to-phenotype approach asks whether a genetic variant described as non-functional or poorly functional is associated with differences in drug clearance. The outcome description refers to “OCT3” genotype, whereas the title and summary refer to OAT3. The registry record does not resolve this naming inconsistency.

This is a question about a measured pharmacokinetic outcome in the enrolled participants. It is not framed as a comparison of clinical outcomes or as a test of treatment benefit. Because genotype defines the comparison and there is no randomized allocation, any observed group difference would be an association in this study, not a randomized estimate of a genotype effect. Numerical results for the outcome and the sizes of the genotype groups are not reported in the registry record.

3. Trial Design

The registry classifies this as a Phase 1, completed, single-group study with allocation marked as not applicable and masking listed as none. Cefotaxime is the intervention. The planned administration is a single IV push of 2 grams over 5 minutes. The study description says participants were stratified by genotype, heterozygous versus homozygous, to examine renal clearance after dosing. Thus, the genotype strata are the comparison of interest, rather than treatment arms created by random assignment.

Enrollment is recorded as 24. The primary outcome timeframe is post dose up to 24 hours. The registry describes the participants as healthy and says the OAT3 Ile305Phe variant was determined to be heterozygous or homozygous for each participant. It does not report how many participants were in either genotype stratum, whether all enrolled participants contributed endpoint data, or whether any participants were excluded from the outcome analysis.

The study start is recorded as 2004-01 and primary completion as 2011-12; its status is completed. The registry lists one outcome measure and zero analyses. It does not report a randomized control group, masking procedures beyond the entry of none, or a detailed statistical analysis plan. These design features matter when interpreting any contrast: genotype groups can differ in characteristics other than the genotype, and the registry does not describe adjustments for such differences. The registry condition entry is “Focus Groups,” while its summary describes healthy participants and a pharmacokinetic question; the record does not explain that entry.

The design can address whether measured clearance differs across the described genotype strata among participants studied. Without reported group-specific results, analysis details, or a control comparison, it cannot establish the size or precision of a genotype association from the information 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.

Before assignment: No wash-out as these were healthy control subjects not currently on any medications.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The OAT3 Ile305Phe variant was determined to be heterozygous or homozygous for each healthy participant.

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 Effect of OAT3 on Renal Secretion of Cefotaxime IV Based on Genotype, measured over post dose up to 24 hours.

The primary endpoint is the mean renal clearance of cefotaxime, reported in mL/min, with standard deviation as the stated measure of dispersion. The measurement is described as being based on urine content of cefotaxime metabolites after a single IV administration. The timeframe is post dose up to 24 hours, and participants are stratified as heterozygous or homozygous for the stated variant.

Renal clearance is used to describe the rate at which a substance is removed from the body by the kidneys, expressed relative to its concentration in the relevant biological measure. In this study’s rationale, comparing clearance across genotype strata is intended to assess whether OAT3 variation is associated with renal secretion of cefotaxime. This is a pharmacokinetic measure; it does not, by itself, describe symptoms, treatment benefit, or other clinical outcomes.

The registry record identifies the endpoint and its summary measure but does not report the group means, standard deviations, a between-group estimate, or its uncertainty. It also does not give further details about how metabolite measurements were converted into the stated clearance measure. Consequently, the endpoint’s intended meaning is clear at a high level, but the magnitude and precision of any genotype-group difference cannot be evaluated from the reported record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean represent?

General explanation: For a continuous outcome, a group mean is the arithmetic average of the measured values in that group. It gives a concise description of the group’s central level, but does not describe how widely individual measurements vary. The registry specifies mean as the primary endpoint parameter and standard deviation as its dispersion measure. Neither group-specific summary is reported, so the record does not allow readers to assess the observed clearance levels or their variability.

What does the standard deviation add?

General explanation: A standard deviation describes the spread of observations around their group mean. A larger spread means observations are more dispersed; a smaller spread means they are more concentrated. It is not the same as the uncertainty in the mean or in a between-group contrast. To assess uncertainty in a comparison, readers would generally need an estimate of the contrast and a suitable uncertainty measure, such as a confidence interval. Such results are not reported in the registry record.

How should a confidence interval be read?

General explanation: A confidence interval gives a range of values compatible with the data and the method used to calculate it. It communicates precision as well as the direction and scale of an estimated contrast. A narrow interval indicates greater precision than a wide interval, under the assumptions of the analysis. It is not a guarantee that the true effect lies within the particular interval. No confidence interval for the genotype comparison is reported in the registry record, so its precision cannot be assessed.

What would a p-value say?

General explanation: A p-value assesses how incompatible the observed data are with a specified null hypothesis under the chosen statistical model. It does not measure the size or clinical importance of a difference, and it is not the probability that the null hypothesis is true. Interpretation also depends on the analysis plan and assumptions. The registry record does not report a p-value, analysis, or detailed testing plan for this endpoint. The planning assumption of a two-sided significance level of 0.05 is not a reported outcome test.

Why does the design affect inference?

General explanation: Random allocation can make treatment groups comparable, on average, with respect to measured and unmeasured baseline characteristics. Here, the registry describes one cefotaxime group stratified by genotype, with allocation marked not applicable. A difference between genotype strata would therefore be observational. Other characteristics associated with genotype or clearance could contribute to a group contrast. Whether such factors were measured or adjusted for is not reported in the registry record.

The record names renal clearance as the outcome, measured using urine content of cefotaxime metabolites after a single IV push. It does not explain the calculation used to derive clearance from those measurements, the timing of individual urine collections, or the approach to any values below measurement limits. Those are relevant details for assessing measurement and analysis, but they are not reported in the registry record.

What does over-dispersion mean?

General explanation: Over-dispersion occurs when observed variability exceeds what an assumed statistical model expects. It is particularly relevant to count data, where simple models may underestimate uncertainty if variation is greater than their assumptions allow. The primary endpoint in this registry is continuous and summarized by a mean and standard deviation; no over-dispersion analysis is reported. The registry record does not provide enough analysis detail to determine whether any particular variance model was used.

How should the planning assumptions be understood?

The registry’s planning statement describes a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. These are planning assumptions, not the trial’s reported design or results. Sample-size calculations under assumptions are planning illustrations; they are not observed power and do not show that a study did or did not detect an effect. The registry record does not report the underlying observed effect or a detailed sample-size justification. It also does not explain the relationship between equal allocation to two arms in the planning statement and the single-group, genotype-stratified study description.

Recalculated estimates, if presented elsewhere, would be simple unadjusted calculations from posted summary statistics rather than the sponsor’s analysis. In this record, the numerical summaries needed to make such a comparison are not reported. No recalculated contrast or precision estimate can therefore be interpreted from the registry outcome entry. When sponsor-reported and recalculated estimates disagree, the sponsor’s own analysis takes precedence; the registry record does not report sponsor outcome estimates for this endpoint.

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("Heterozygous for the Ile305Phe Variant", "Homozygous for OAT3-Ile305Phe Variant")
n   <- c(12, 12)
m   <- c(84.8, 158)
sp  <- c(32.1, 44.1)
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  Heterozygous for the Ile305Phe Variant  12  84.800  32.100  64.405  105.195
CARM  Homozygous for OAT3-Ile305Phe Variant  12  158.000  44.100  129.980  186.020

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a hierarchy of endpoints, or procedures for controlling multiplicity. Multiplicity arises when several outcomes, time points, subgroups, or statistical tests are examined; repeated testing can increase the chance of finding a nominally unusual result by chance. The registry record does not provide enough information to determine whether any additional analyses were conducted outside the posted record, and no such analyses should be inferred from the outcome listing.

The primary endpoint is described as mean renal clearance, with standard deviation, comparing heterozygous and homozygous genotype strata. Although the timeframe is stated as post dose up to 24 hours, the record does not explain whether the endpoint is a single summary over that timeframe or whether measurements at multiple times were analyzed separately. The number of observations entering the endpoint analysis and the handling of missing measurements are also not reported in the registry record.

There is no reported analysis population, no account of exclusions, and no indication of whether all enrolled participants contributed data. The registry enrollment is 24, but that entry should not be treated as the number analyzed for the endpoint or as the size of either genotype group. The record also does not report imputation methods, sensitivity analyses, or how incomplete urine or metabolite measurements would be handled. These omissions limit assessment of the endpoint’s completeness and the robustness of any comparison.

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 registry reports the Cefotaxime group with 24 participants at risk for serious adverse events and 0 affected. This is a count of serious adverse events recorded for that group in the registry; it is not a complete description of every possible safety outcome. The record lists no top serious-event terms. The death field is null, which means a death count is not reported in the registry record; it should not be read as a reported count of zero.

These figures describe what the registry records, not proof that no adverse events occurred. The record does not provide detail about non-serious events, event definitions, severity grading, observation procedures, or the timing of safety collection. Nor does it provide a comparator group suitable for a like-for-like safety comparison: allocation is not applicable and the study is described as single-group. The serious-event count should therefore be read narrowly as a registry-reported count, rather than as a broad assessment of safety or a comparison of risks.

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

The registry record establishes that a completed Phase 1 study was designed to examine cefotaxime renal clearance across OAT3 genotype strata. It specifies a single IV administration, a continuous mean endpoint in mL/min, standard deviation as the dispersion measure, and a post-dose timeframe up to 24 hours. These details describe the intended question and measurement, not the observed result.

Numerical endpoint results are not reported in the registry record. There are no group means, standard deviations, contrast estimates, confidence intervals, or p-values in the outcome information. Thus the record does not show whether clearance was higher or lower in either genotype group, how large any difference was, or how precisely it was estimated. The enrollment entry does not indicate how many participants contributed measurements or how many belonged to each stratum.

Even if a group difference were reported, this design would support an observational comparison across genotype strata, not a randomized causal estimate. A difference could be associated with genotype, but interpretation would depend on the analysis and on other factors that might relate to clearance. The registry record does not report adjusted analyses or enough participant-level detail to evaluate those issues.

The posted serious-adverse-event entry records 0 affected among 24 at risk in the Cefotaxime group, while the death count is not reported. Those entries are limited safety counts and do not replace detailed safety reporting. Overall, the registry supports a description of the study’s aim and design, but not a conclusion about the size or direction of its primary endpoint result.

14. Why This Trial Matters Statistically

This study is statistically interesting because it frames a pharmacokinetic question around genetic variation. Rather than comparing randomized treatment assignments, it compares participants stratified by a transporter genotype after the same stated cefotaxime administration. That distinction illustrates how the scientific question and design determine what an estimated contrast can mean: genotype-group differences are associations in the studied participants, not automatically causal effects.

The endpoint also illustrates the value of distinguishing a group average from its uncertainty and variability. Mean renal clearance is the stated primary measure, and standard deviation is the stated description of dispersion. Those summaries would help characterize the data, while an estimated group contrast and confidence interval would communicate the comparison and its precision. The registry record identifies these intended measures but does not report their numerical values, so the statistical question is visible while its empirical answer is not.

The record also demonstrates why enrollment is not a substitute for an analysis population. It lists enrollment as 24, but does not give genotype-specific group sizes, the number with usable outcome measurements, or exclusions. Without those details and the endpoint results, readers cannot assess how much information supports the comparison.

Finally, the mismatch between the single-group genotype-stratified description and the separate planning assumptions of equal allocation between two arms makes it important to distinguish study design from planning illustrations. Assumptions used for planning are not evidence of observed power or a substitute for reported analyses. The case highlights the statistical value of complete outcome estimates, uncertainty measures, analysis-population details, and a transparent account of how the planned comparison was conducted.

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 main limitation for interpreting this record is that numerical primary outcome results are not reported. Without group-specific means, standard deviations, a contrast estimate, or a measure of uncertainty, the direction, magnitude, and precision of the genotype comparison cannot be assessed. The registry lists zero analyses, and it does not provide an analysis plan or detailed model description.

The record gives enrollment as 24 but does not report the number of participants in each genotype stratum, the number contributing endpoint measurements, or any exclusions. It does not describe missing-data handling, measurement completeness, or whether all participants were followed through the stated post-dose timeframe. These gaps prevent assessment of the information available for the comparison.

The design is single-group and not randomized; the genotype strata are not treatment arms created through allocation. The registry does not report adjusted estimates or information about potential confounding. The endpoint description also uses “OCT3” where the study title and summary use OAT3, and the record does not clarify that terminology. Its condition entry, “Focus Groups,” is not explained alongside the summary’s description of healthy participants and a pharmacokinetic study.

Further limitations include the absence of reported details on the calculation of renal clearance from urine metabolite measurements and on safety outcomes beyond the posted serious-event count. The planning statement describes equal allocation between two arms, while the study is described as single-group with genotype stratification; the registry does not explain this difference.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of, OAT3, on the Renal Secretion of Cefotaxime — NCT00187655.
• Registry record last updated 2014-10-29; status last verified 2014-10.
• Results first posted 2014-05-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

The registry describes a completed Phase 1, single-group study of cefotaxime and OAT3 genotype. It records enrollment as 24 and describes a single IV push of 2 grams over 5 minutes. The primary endpoint is mean renal clearance in mL/min, with standard deviation, measured from urine content of cefotaxime metabolites post dose up to 24 hours and compared across heterozygous and homozygous genotype strata.

The record lists one outcome measure and zero analyses, but does not report numerical endpoint results, genotype-group sizes, or a statistical analysis plan. The Cefotaxime group has 24 participants at risk and 0 affected by serious adverse events in the registry entry; the death count is not reported. The record supports a description of the study question and design, but not an estimate of the primary comparison.