Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics (NCT00768716), a non-randomized phase 4 study. The primary outcome is Acetaminophen Plasma Clearance Association With Race/Ethnicity.

2. Clinical Question

The registry record identifies the study as an investigation of acetaminophen pharmacokinetics, rather than a trial designed to compare clinical benefit. Its stated motivation was to examine whether race/ethnicity and selected genes might be related to differences in acetaminophen disposition. The listed conditions are pain, fever and hepatotoxicity, but the primary endpoint is a pharmacokinetic measure, not a clinical outcome measuring pain relief, fever reduction or liver injury.

The specific clinical question that can be evaluated from the posted record is whether the groups differed in measured plasma clearance after the dose. The observed clearance values, group estimates and statistical comparison are not reported in the registry record, so the direction, size and precision of any group difference cannot be established from this record.

3. Trial Design

This was a completed phase 4 study sponsored by Tufts University. The registry lists a start date of 2008-12 and a primary completion date of 2012-06. Its design is described as parallel, non-randomized and unmasked. The registry reports enrollment of 95.

Participants were categorized into White subjects and Black subjects. Both arms received the same listed intervention: 2 x 500 mg acetaminophen by mouth once. Because allocation was non-randomized, the groups were not formed by random assignment. Differences between the groups could reflect characteristics other than the group label, and the registry itself warns that the arms are not a like-for-like control comparison. The record does not report adjustment methods that would address such differences.

The study summary states that the investigators aimed to measure acetaminophen elimination through glucuronidation, sulfation and oxidation, and to correlate those rates with selected polymorphisms in UGT1A6, SULT1A1 and CYP2E1. It describes hypotheses about faster glucuronidation in African-Americans than White-Americans and associations between the pathways and the corresponding genes. These are stated aims and hypotheses, not findings; their results are not reported in the registry record.

The summary describes a plan to include 100 self-identified White-Americans and 100 African-Americans, whereas the enrollment field reports 95. The record does not explain the difference or report how many participants were included in each endpoint analysis. It also does not report eligibility criteria, recruitment procedures, the statistical analysis plan, sample-size justification for the actual study, interim analyses, or details of masking beyond the designation of none.

The registry lists 7 outcome measures and 6 analyses, but their full results and analysis details are not present in the information recorded for this study. Consequently, the design description establishes the question and treatment exposure, but not the numerical evidence needed to judge the primary comparison.

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

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 Acetaminophen Plasma Clearance Association With Race/Ethnicity, measured over 2 days.

The primary endpoint is acetaminophen plasma total clearance, measured in mL/min/kg. The registry describes the measurement as plasma total clearance measured by HPLC, with a timeframe of 2 days. The endpoint is reported using a median and inter-quartile range as its planned summary format. The actual group values and ranges are not reported in the registry record.

Clearance is a pharmacokinetic measure of the rate at which a substance is removed from plasma relative to its concentration. In general, clearance helps characterize drug disposition; it is not itself a direct measure of symptom relief, toxicity or overall clinical benefit. Scaling clearance by body weight allows the measure to be expressed relative to weight, as reflected in the stated unit.

The study summary focuses on three pathways of acetaminophen elimination: glucuronidation, sulfation and oxidation. Total plasma clearance is the primary endpoint, while pathway-specific elimination and genetic associations are part of the stated study aims. The record does not give pathway-specific estimates, assay details beyond HPLC for the primary endpoint, or the numerical results needed to determine whether the groups differed. Interpretation should therefore remain limited to the endpoint definition and the stated measurement timeframe.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is described as a median with an inter-quartile range. These summaries are commonly used when a measure is skewed or when a few extreme observations could substantially affect a mean. The median gives the midpoint of the ordered observations; the inter-quartile range describes the spread of the central half of those observations. This is a general explanation of the statistics, not a claim about the observed distribution in this study. The registry does not report the actual median or inter-quartile range for either group.

What does clearance measure?

In general, clearance relates the rate at which a drug is removed from plasma to its plasma concentration. It provides a way to describe drug disposition, and the unit mL/min/kg expresses the measure relative to body weight. It is distinct from a clinical endpoint such as symptom improvement or an adverse clinical outcome. The registry describes plasma total clearance measured by HPLC and gives a timeframe of 2 days. It does not report the detailed measurement schedule, assay validation information, or the observed values.

Why does the non-randomized comparison matter?

Random allocation is used in many clinical trials to make groups more comparable, on average, with respect to both observed and unobserved characteristics. This study is recorded as non-randomized. Race/ethnicity group membership was not assigned as a treatment, and the comparison is observational in that respect. In general, differences in clearance between groups could reflect factors associated with group membership as well as any biological associations under study. Statistical adjustment may address measured covariates, but it cannot automatically remove confounding from unmeasured factors. The registry record does not report the adjustment strategy, so the extent to which confounding was considered cannot be assessed.

How should an estimate and confidence interval be read?

In general, an effect estimate gives the size and direction of a contrast, while a confidence interval shows the range of values reasonably compatible with the data and the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval. A confidence interval is not a guarantee that the true effect lies within its bounds, and statistical compatibility does not by itself establish clinical importance. No effect estimate or confidence interval for the primary comparison is reported in the registry record, so precision cannot be judged for this endpoint.

What can a p-value establish?

In general, a p-value describes how unusual data at least as incompatible with a specified null model would be, if that model and the test assumptions were correct. It does not measure the probability that a hypothesis is true, the size of an effect, or its importance. The registry record does not report a p-value for the primary endpoint or the genetic analyses. It also does not describe the tests used, their assumptions, or whether analyses were adjusted for covariates.

How does multiplicity relate to the study aims?

Testing several endpoints, pathways or genetic associations can increase the chance of obtaining at least one apparently notable result by chance. General approaches to multiplicity include adjusting the significance threshold or treating analyses as exploratory, but the appropriate approach depends on the protocol and analysis plan. The record lists 7 outcome measures and 6 analyses, yet does not identify the full set of comparisons or report a multiplicity strategy. No particular correction or interpretive hierarchy can therefore be attributed to the study.

What do the planning assumptions mean?

The registry describes sample-size planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation between arms and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect. Such illustrations describe hypothetical planning under specified assumptions; they are not observed power and do not show how the actual study was designed. The record does not report a sample-size justification for the trial's own design. No planning values are stated in the information recorded for this study, so no numerical planning result can be interpreted.

10. Multiplicity, Missing Data and Analysis Populations

The registry records 7 outcome measures and 6 analyses, but does not identify the full analysis set, specify which outcomes were primary or secondary beyond the named primary endpoint, or report how multiplicity was handled. The study summary describes multiple pathway and genetic hypotheses. When several outcomes or associations are tested, the chance of at least one apparently notable finding can increase. In general, a prespecified testing hierarchy or adjustment can help control this issue, but the registry record does not report whether either approach was used.

The record does not report the number of participants contributing to the primary endpoint or to each analysis. Although enrollment is reported as 95, the study summary describes planned groups of 100 each; the registry does not explain the difference. Missing-data counts, reasons for missingness, imputation methods and sensitivity analyses are not reported in the registry record. It is therefore not possible to assess whether missing observations affected the estimates or whether the analyzed participants differed from those enrolled.

Analysis-population definitions are also not reported in the registry record. The record does not state whether analyses used all enrolled participants, participants who received the dose, or a subset with available pharmacokinetic or genetic measurements. The statistical analysis plan, interim analyses and handling of protocol deviations are not reported. These omissions limit reproducibility and make it difficult to determine how closely the posted results, if any, would correspond to the stated hypotheses. The registry's sample-size illustrations are planning exercises and should not be interpreted as observed power or as documentation of the study's actual design justification.

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.

The registry lists serious adverse event counts for White Subjects and Black Subjects. It reports 0 serious events among 54 at risk in the White Subjects group and 0 among 41 at risk in the Black Subjects group. It reports 0 other adverse events in each group and 0 deaths in each group. No top serious adverse event terms are listed.

These figures describe the events recorded in the registry for the listed groups. They do not establish that an event is impossible, nor do they by themselves quantify comparative safety. In general, a zero observed count does not prove the absence of risk, particularly when the number of observed participants and the observation period are limited. The registry identifies a timeframe of 2 days for the primary endpoint, but does not give a separate safety follow-up duration or detailed adverse-event collection methods. The record also does not report event definitions, severity grading, or whether all participants were assessed for safety. The safety counts should therefore be read as registry-reported event counts, not as a comprehensive demonstration of safety or as a randomized comparison between groups.

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

The registry record establishes that this completed study examined acetaminophen pharmacokinetics in White subjects and Black subjects after a single oral dose. Its primary endpoint was plasma total clearance, measured in mL/min/kg and described as a median with an inter-quartile range over 2 days. The study summary also set out questions about three elimination pathways and selected genetic polymorphisms.

The record does not report the primary endpoint values, a group contrast, confidence intervals or p-values. It also does not report the outcomes of the pathway or genetic analyses. Consequently, the posted information does not establish whether clearance differed between the groups, whether the stated hypotheses were supported, or how precisely any associations were estimated. It cannot support a conclusion about the clinical effects of acetaminophen, pain relief, fever reduction or hepatotoxicity; those are not the numerical results reported for the primary endpoint.

Even if a group difference were reported, the non-randomized design would require cautious interpretation. The groups were not randomly assigned, and the registry cautions that they are not a like-for-like control comparison. A measured association would not by itself show that race/ethnicity or a particular gene caused a difference. The record does not give enough information about covariate adjustment, missing data or analysis populations to evaluate those issues.

The appropriate conclusion from the registry record is therefore limited: it describes a pharmacokinetic study and its intended questions, but does not include the outcome statistics needed to judge the findings. Study completion and stated hypotheses should not be mistaken for evidence that those hypotheses were confirmed or rejected.

13. Why This Trial Matters Statistically

This study is statistically notable because it connects a pharmacokinetic endpoint with questions about both group differences and genetic variation. The registry describes an intended analysis of acetaminophen elimination through glucuronidation, sulfation and oxidation, alongside selected polymorphisms in genes involved in metabolism. Such questions illustrate the distinction between measuring a drug-disposition outcome and establishing an association with participant characteristics.

The design also highlights why observational group comparisons need careful interpretation. Non-randomized groups may differ in characteristics beyond the categories used to define them. A statistical association between group membership and clearance would not alone identify a mechanism or establish causality. Clear reporting of participant characteristics, covariate adjustment, analysis populations and uncertainty would be important for evaluating such a comparison, but these details are not reported in the registry record.

The endpoint's stated median and inter-quartile range also foreground the importance of describing the distribution of pharmacokinetic measurements, rather than relying only on a single summary. In general, reporting both a measure of center and spread can help readers understand heterogeneity and the precision of group comparisons. Here, however, the observed summaries and uncertainty measures are not reported in the registry record.

Finally, the record illustrates that a completed status and a detailed set of research aims do not substitute for posted estimates. Without numerical findings, readers cannot assess effect size, precision, multiplicity or the degree to which the planned questions were answered. Transparent reporting of those details is central to statistical interpretation.

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 main limitation for interpretation is that the registry record does not report numerical results for the primary endpoint. Group medians, inter-quartile ranges, effect estimates, confidence intervals and p-values are absent. The pathway-specific and genetic association results described in the study summary are also not reported. Thus, the record allows the study question and endpoint to be described but does not allow the findings to be evaluated.

The study was non-randomized and unmasked. The registry cautions that the arms are not a like-for-like control comparison. The record does not report covariate adjustment, participant characteristics that might affect clearance, or sensitivity analyses. These omissions prevent assessment of confounding and robustness. The record also does not reconcile enrollment of 95 with the study summary's plan for 100 participants in each group.

Analysis denominators and analysis-population definitions are not reported, nor are missing-data counts, reasons for missingness or methods for handling unavailable measurements. The record does not give detailed eligibility criteria, recruitment information, assay procedures beyond HPLC for the primary endpoint, or a separate safety follow-up duration. It also does not report the statistical analysis plan, a study-specific sample-size justification, interim analyses or multiplicity handling. These limitations concern what can be learned from the registry record; they do not establish that a particular procedure was or was not used outside what the record reports.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Race/Ethnicity and Genes on Acetaminophen Pharmacokinetics — NCT00768716.
• Registry record last updated 2019-05-23; status last verified 2019-05.
• Results first posted 2019-05-08.
• 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

NCT00768716 is a completed phase 4, parallel, non-randomized and unmasked study sponsored by Tufts University. The registry reports enrollment of 95 and lists a start date of 2008-12 and primary completion date of 2012-06. White subjects and Black subjects received 2 x 500 mg acetaminophen by mouth once.

The primary endpoint was acetaminophen plasma total clearance, measured in mL/min/kg and described as a median with an inter-quartile range over 2 days. The study summary describes planned investigation of glucuronidation, sulfation, oxidation and selected genetic polymorphisms. Numerical results for the primary endpoint and the stated pathway and genetic questions are not reported in the registry record. Serious adverse events, other adverse events and deaths are listed as 0 in each group. The registry cautions that the non-randomized arms are not a like-for-like control comparison.