This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Acetaminophen Adduct Formation in Non-Drinkers Taking Therapeutic Doses of Acetaminophen for Ten Consecutive Days (NCT00616018), a non-randomized phase 4 study. The primary outcome is Serum Level of Acetaminophen-cysteine (APAP-Cys) Protein Adducts.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00616018 |
| Phase | Phase 4 |
| Condition | Drug Induced Liver Injury |
| Allocation | Non-Randomized |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 35 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Kennon Heard |
| Results posted | Yes |
2. Clinical Question
The study asks whether acetaminophen-cysteine (APAP-Cys) protein adducts can be measured in the serum of alcohol-abstaining people taking therapeutic doses of acetaminophen for ten consecutive days, and how the measured concentrations vary across the study visits. The registry describes the purpose as measuring adduct formation in healthy people who do not drink alcohol. It lists serum APAP-Cys adduct concentration as the primary outcome.
The intervention was acetaminophen at 4 g/day for ten consecutive days. Measurements were scheduled at Day 0, 4, 7, 9, 11, and 14. The primary outcome population is described as the 24 participants who completed all study visits. Alanine aminotransferase (ALT) is listed as a secondary outcome, but its result is not reported in the registry record.
This is a single-group study, not a comparison of acetaminophen with a concurrent untreated or alternative-treatment group. Its question is therefore descriptive: what adduct concentrations were measured over time among the participants included in the outcome analysis? The record does not give the actual concentrations, means, or standard deviations for any visit, so it cannot establish the size or pattern of change from the posted results alone. It also cannot distinguish changes associated with the study regimen from changes that might have occurred for other reasons.
The registry record identifies the study as Phase 4 and reports 35 participants enrolled. It does not report a randomized comparison, a control group, or an analysis comparing groups. The results should be understood within those limits: the central endpoint is a measured biological marker, and its numerical findings are not reported in the registry record.
3. Trial Design
The study is recorded as a Phase 4, non-randomized, open-label, single-group trial. Its status is completed. The registry lists 35 participants enrolled. All subjects in the described arm received acetaminophen at 4 g/day for ten consecutive days. Because the design has one group and no masking, participants and investigators were not assigned to blinded treatment groups, and there is no concurrent control group for a like-for-like comparison.
The title and study description concern alcohol-abstaining participants; the brief summary describes healthy people who do not drink alcohol. The listed condition is Drug Induced Liver Injury, but that listing alone does not establish that participants had liver injury. Specific eligibility criteria and further descriptions of the enrolled population are not reported in the registry record.
The primary outcome was serum APAP-Cys protein-adduct concentration, measured at Day 0, 4, 7, 9, 11, and 14. The primary analysis population is described as the 24 participants who completed all study visits. The registry also lists ALT as a secondary outcome and reports two outcome measures overall, but gives no ALT results. It records no analyses in the analysis count.
The registry does not report a control arm, random allocation, an allocation concealment procedure, a formal sample-size justification, or the statistical plan used for the original study. These omissions limit what can be concluded about the study's design rationale and analysis procedures. Planning illustrations based on a two-arm design are not a description of this single-group trial's actual allocation or original design. They should not be mistaken for evidence that the study randomized participants or included a comparator.
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: Thirty-five subjects were consented for the study. Of these, eight were excluded (six did not meet inclusion criteria and two refused to participate). The 27 eligible subjects were assigned to the treatment arm to receive 4 grams of acetaminophen per day, for 10 consecutive days.
Overall Study
| Stage | Acetaminophen |
|---|---|
| STARTED | 27 |
| COMPLETED | 24 |
| NOT COMPLETED | 3 |
Reasons for not completing this period:
| Reason | Acetaminophen |
|---|---|
| Protocol Violation | 3 |
Analysis population for the primary outcome, as defined in the registry: Analysis is based upon the 24 subjects who completed all study visits.
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.
| Characteristic | Unit | Acetaminophen |
|---|---|---|
| Participants analysed | 27 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 27 |
| Age, Categorical: >=65 years | Participants | 0 |
| Age Continuous | years | 37.3 (SD 12.2) |
| Sex: Female, Male: Female | Participants | 19 |
| Sex: Female, Male: Male | Participants | 8 |
| Region of Enrollment: United States | participants | 27 |
6. Primary Endpoint
The registry lists the primary outcome as Serum Level of Acetaminophen-cysteine (APAP-Cys) Protein Adducts, measured over Day 0, 4, 7, 9, 11, and 14..
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | nmol/mL |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the serum concentration of acetaminophen-cysteine (APAP-Cys) protein adducts, expressed in nmol/mL. According to the registry description, some acetaminophen is processed in the liver and can bind to proteins; the resulting product is called an adduct. Measuring APAP-Cys adduct concentrations therefore provides a way to quantify this particular biological product during the study regimen and at scheduled visits after the ten-day dosing period.
The registry specifies measurements at Day 0, 4, 7, 9, 11, and 14, and identifies the reported summary measure as a mean with standard deviation. In general, a mean describes the central level of measurements, while a standard deviation describes their spread around that mean. Reporting both can help readers understand the observed concentration level and how much individual measurements varied.
The endpoint is a laboratory marker, not a direct measure of symptoms or clinical outcomes. Its interpretation depends on the actual measured values and on the study population and design. The numerical means and standard deviations for the scheduled visits are not reported in the registry record. As a result, the record identifies what was measured and when, but does not allow readers to assess the observed concentration levels or their variability.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record establishes the structure of the primary outcome assessment but does not report the primary outcome values. Serum APAP-Cys adduct concentration was measured at six scheduled visits, and the stated analysis population comprises 24 participants who completed all study visits. The record identifies the outcome as a mean with standard deviation, but gives no mean or standard deviation for any visit. Consequently, the direction, magnitude, and variability of the observed concentrations cannot be described from the posted results.
The timing permits assessment of measurements before, during, and after the ten consecutive days of acetaminophen dosing. That schedule alone does not demonstrate a rise, fall, peak, or return toward an earlier level. Such a description would require the actual measurements or reported summary statistics, which are not reported in the registry record. Nor can a change between visits be quantified from the information available.
The single-group, open-label design is important to interpretation. The study records measurements among participants receiving acetaminophen, but does not include a concurrent comparison group. It therefore cannot isolate the regimen's contribution from other explanations for any observed time pattern. This is a limitation of the design, not a reason to infer that no change occurred.
The registry reports 35 participants enrolled, while the primary outcome population is the 24 participants who completed all study visits. These figures describe different stages of participation. The record does not explain why participants were not included in the completed-visits analysis, whether measurements were available for some visits among those participants, or whether a missing-data method was used. The primary results therefore cannot be assumed to represent all enrolled participants.
ALT is listed as a secondary outcome, but its result is not reported in the registry record. No analysis records are listed. The registry also does not report confidence intervals or p-values for the primary endpoint. General statistical interpretation: a confidence interval conveys uncertainty around an estimate, while a p-value summarizes compatibility of data with a specified null model; neither can be evaluated when their values and the underlying outcome summaries are absent. The available record supports description of the protocol's measurement schedule and analysis population, not a conclusion about the observed concentration levels or their precision.
9. Statistical Methods Explained
The registry identifies the primary outcome as a continuous measure: serum APAP-Cys protein-adduct concentration in nmol/mL. It names the mean as the summary statistic and the standard deviation as the measure of dispersion. The outcome was measured at Day 0, 4, 7, 9, 11, and 14, while the primary analysis is described as involving the 24 participants who completed all study visits. The numerical summaries themselves are not reported in the registry record.
What does a mean describe?
General explanation: a mean is the arithmetic average of a set of measurements. For a continuous laboratory outcome, it gives a concise description of the central level in the group being summarized. It does not show the full distribution. Different patterns of individual measurements can share the same mean, so the mean is best read alongside a description of spread and the number of observations contributing to it.
The registry specifies a mean at the outcome level but does not state whether any particular longitudinal comparison or model was used to analyze repeated measurements. A sequence of visit-specific means can describe the group's measurements over time, but it does not by itself provide an inferential test of change or account for the fact that measurements from the same participant are related. The specific analysis procedure is not reported in the registry record.
What does the standard deviation add?
General explanation: the standard deviation describes how dispersed individual measurements are around the mean. A smaller standard deviation indicates measurements clustered more closely around that mean; a larger one indicates more spread. It is not the same as a confidence interval. The standard deviation describes variation among measurements, whereas a confidence interval describes uncertainty in an estimated quantity under a statistical procedure.
The registry names standard deviation as the dispersion measure but does not give its values. Readers therefore cannot assess whether measurements were tightly clustered or widely spread at any visit. The record also does not report confidence intervals for the means. Even if a mean were available, precision would not be fully conveyed by the mean alone.
Why do repeated measurements matter?
General explanation: measurements taken from the same participant at several visits are usually correlated, because each participant contributes a series of observations. Analyses of repeated measurements can account for that dependence. Treating every measurement as if it came from a different participant would ignore within-person structure. The registry specifies repeated visits but does not report whether the original analysis used a repeated-measures method, a longitudinal model, or another approach.
The stated primary population consists of participants completing every visit. This is a complete-visit analysis population as described in the record. It does not establish that all enrolled participants had data at each visit or explain how incomplete records were handled. The method for handling missing measurements is not reported in the registry record.
How should planning calculations be distinguished from trial analysis?
The record includes assumptions for a planning illustration based on an observed effect: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. This is a planning illustration, not the design of the actual single-group trial. Its two-arm assumption does not change the registry's description of a non-randomized, single-group study. No numerical sample-size illustration values are reported in the record presented for this analysis, and the observed effect needed for such calculations is not reported in the registry record.
General explanation: sample-size calculations describe planning under specified assumptions. They are not a measure of the probability that a completed study has found a true effect, and an illustration should not be described as observed power. In this case, the planning assumptions should not be interpreted as the original trial's rationale because the record does not report the trial's own sample-size justification.
What cannot be inferred from the analysis record?
The registry lists zero analyses and does not report outcome means, standard deviations, confidence intervals, or p-values. It also does not report a detailed statistical analysis plan, adjustment for repeated observations, covariate adjustment, or methods for handling missing data. These details should not be inferred from the measurement schedule or the stated summary statistic. General statistical explanation can clarify what common methods mean, but it cannot substitute for the study's unreported analysis choices or results.
10. Multiplicity, Missing Data and Analysis Populations
The primary endpoint was scheduled at Day 0, 4, 7, 9, 11, and 14, and ALT is listed as a secondary outcome. Multiple visits and more than one outcome raise general questions about multiplicity: when several outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase if each is assessed separately. This is a general statistical consideration, not evidence that the study performed a particular set of tests. The registry does not report a multiplicity adjustment or describe which visit-to-visit comparisons, if any, were planned.
The primary analysis population is described as 24 participants who completed all study visits, compared with 35 enrolled participants. The record does not give reasons for non-completion or explain whether data from participants without all visits were used in any other way. It does not describe imputation, a missing-data model, or a sensitivity analysis. The approach to missing data is therefore not reported in the registry record.
General explanation: excluding participants without complete records can produce a result that differs from one based on all enrolled participants if completion is related to the outcome. This possibility cannot be assessed without information about missingness and the excluded participants. It should not be assumed that missing values were either harmless or systematically different.
The record lists two outcome measures overall and zero analyses, but does not present numerical results for either the primary outcome or ALT. It also does not report a prespecified analysis population beyond the description of the 24 completers for the primary outcome. Details about any intention-to-treat, per-protocol, or other analysis populations are not reported in the registry record. These gaps make it difficult to assess how fully the reported analysis corresponds to the intended study question.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Acetaminophen | 0 | 27 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Acetaminophen | 12 of 27 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Acetaminophen |
|---|---|---|
| nausea | Gastrointestinal disorders | 5 of 27 |
| headache | Nervous system disorders | 3 of 27 |
| diarrhoea | Gastrointestinal disorders | 2 of 27 |
| fatigue | General disorders | 2 of 27 |
| migraine | Nervous system disorders | 2 of 27 |
The adverse-event figures identify 27 participants at risk in the acetaminophen group. The posted results record zero participants affected by serious adverse events and 12 affected by other adverse events. These are counts for the listed group; the registry does not provide event descriptions for the other adverse events. No serious adverse-event terms are listed. Deaths are not reported in the registry record.
These figures should be read as safety reporting within this study, not as a comparison of risks between treatments. There was one study group and no concurrent control group. The figures therefore do not establish whether events were caused by acetaminophen, nor do they show how the same participants might have fared under another regimen. The record also does not give details about event severity, timing, duration, or participant-level overlap among event categories.
The safety denominator of 27 differs from the 24 participants described as completing all primary-outcome visits and the 35 enrolled participants. The registry does not explain that difference. Counts of participants affected do not by themselves convey the full clinical context or the completeness of safety follow-up. The absence of listed serious events in this record should not be interpreted as proof that serious events are impossible or that the study can rule out uncommon events.
12. What the Result Does, and Does Not, Mean
This study is relevant to a specific measurement question: the registry describes serial serum APAP-Cys adduct assessment in alcohol-abstaining participants receiving acetaminophen at 4 g/day for ten consecutive days. It identifies the endpoint, unit, visit schedule, and complete-visit analysis population. These design details help define what the intended observations concern.
However, the registry does not report the numerical primary outcome results. It is therefore not possible to state the measured adduct concentrations, their variability, or how they differed across visits. The record does not establish whether concentrations rose, fell, or stayed similar. ALT is listed as a secondary outcome, but its results are also not reported.
The single-group design also limits what can be attributed to the regimen. Without a concurrent comparison group, any pattern observed in a treated group could not be separated from other influences using this design alone. The study is not a randomized comparison, and its planning illustration assumptions involving two arms do not alter that fact.
General statistical explanation: a measured biomarker can help describe biological observations, but it is not automatically equivalent to a clinical outcome. A biomarker's clinical meaning depends on evidence relating its levels to outcomes that matter to patients; such evidence is not reported in this registry record. The endpoint should therefore be interpreted as a laboratory measurement rather than as direct evidence about symptoms, diagnosis, or treatment benefit.
The posted safety figures record zero participants with serious adverse events and 12 with other adverse events among 27 at risk. They are descriptive counts in a single group, not comparative estimates of treatment risk. Taken together, the registry provides useful design and measurement information, but not the outcome values needed to characterize adduct levels or draw conclusions about their precision and clinical implications.
13. Why This Trial Matters Statistically
Statistically, this study illustrates the distinction between specifying an outcome and reporting its results. The registry gives a clearly named continuous endpoint, units, a visit schedule, and a summary measure of mean with standard deviation. Those details identify what investigators intended to measure. Yet without the numerical summaries, readers cannot assess the observed levels, variation, or time pattern.
The study also highlights why design determines the scope of an inference. A single-group series of measurements can describe observations among participants in that group, but it cannot provide the same comparative evidence as a randomized, concurrent-control design. This matters when interpreting any apparent temporal change: the design alone does not identify what caused it.
The stated analysis population is another important statistical detail. The primary outcome analysis is based on 24 participants who completed all visits, whereas 35 participants were enrolled. A clear account of participant flow and missing-data handling would help readers judge how the analyzed group relates to the enrolled group. Those explanations are not reported in the registry record.
Finally, the record allows readers to distinguish an actual study design from planning assumptions. Its planning illustration uses a two-arm framework, while the trial itself is recorded as single-group and non-randomized. Keeping those roles separate prevents a planning calculation from being mistaken for a trial comparison or an observed finding. The main statistical lesson is that design, analysis population, outcome definition, and numerical results each answer different questions; the registry record contains some of these elements but not the primary numerical findings.
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 most direct limitation for interpreting this study record is that no numerical primary outcome values are reported. Although the registry specifies serum APAP-Cys concentrations, measurement days, units, and a mean with standard deviation, it gives no visit-specific means or standard deviations. The primary result's magnitude and precision therefore cannot be assessed. ALT is listed as a secondary outcome, but its result is not reported in the registry record either.
The trial is non-randomized, open-label, and single-group. There is no concurrent comparator, so the design cannot establish whether any time pattern in the endpoint was attributable to the regimen rather than other factors. The record does not report a detailed protocol, eligibility criteria, or a rationale for the chosen design. The condition listing should not be taken as evidence that all participants had Drug Induced Liver Injury.
The outcome population includes 24 participants who completed all study visits, while enrollment is 35. The reasons for the difference, availability of partial measurements, and missing-data methods are not reported in the registry record. It is therefore unclear how incomplete participation may affect the analysis. The safety count uses 27 participants at risk, and the record does not explain how that group relates to enrollment or outcome completion.
The statistical analysis plan is not reported. The registry lists no analyses and does not provide inferential statistics, confidence intervals, or information about repeated-measures methods or multiplicity. The posted planning assumptions describe an illustration rather than the trial's own design or sample-size justification. These limitations concern what can be learned from the registry record and do not establish that the unreported analyses or procedures were absent from the study itself.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Acetaminophen Adduct Formation in Non-Drinkers Taking Therapeutic Doses of Acetaminophen for Ten Consecutive Days — NCT00616018.
- Registry record last updated 2012-07-12; status last verified 2012-07.
- Results first posted 2012-07-12.
- 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.
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18. Record Summary
The record describes a completed Phase 4, open-label, non-randomized, single-group study with 35 participants enrolled. All subjects in the described arm received acetaminophen at 4 g/day for ten consecutive days. The primary endpoint was serum APAP-Cys protein-adduct concentration in nmol/mL, scheduled at Day 0, 4, 7, 9, 11, and 14. The primary outcome population is described as the 24 participants who completed all visits; mean and standard deviation are named as the summary measures.
ALT is listed as a secondary outcome. The registry reports zero analysis records and does not report numerical results for the primary endpoint or ALT. Safety figures list 27 participants at risk, zero affected by serious adverse events, and 12 affected by other adverse events; deaths are not reported in the registry record. With no comparator and no primary outcome values, the record supports description of the study's design and intended measurements, but not a numerical account of adduct concentrations or a comparative treatment conclusion.