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 A Long-term Efficacy and Safety Study of Tramadol Hydrochloride Plus Acetaminophen (JNS013) in Japanese Participants With Chronic Pain (NCT00736957), a na phase 3 study. The primary outcome is Change From Baseline in Visual Analogue Scale (VAS24) Score at Week 4.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00736957 |
| Phase | Phase 3 |
| Condition | Chronic Pain |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 219 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Janssen Pharmaceutical K.K. |
| Results posted | Yes |
2. Clinical Question
The study asked whether long-term administration of tramadol hydrochloride plus acetaminophen (JNS013) could be evaluated for efficacy and safety in participants with chronic pain. The primary outcome was the change from baseline in the Visual Analogue Scale score for pain over the last 24 hours at Week 4. The record describes the scale and the direction of improvement, but it does not report the observed change, its variability, or an inferential result. The question therefore has to be read as the study’s measurement objective, not as evidence of a treatment effect.
Population
Japanese participants with chronic pain were enrolled. The primary-outcome population was the full analysis set: eligible participants who received study medication and had at least one post-treatment efficacy assessment.
Intervention
The study administered tramadol hydrochloride plus acetaminophen, identified as JNS013. The registry describes the study as evaluating long-term administration, while the primary endpoint was assessed at Week 4.
Comparator
There was no separate comparator group in the registry design. This was a single-group study, so the record does not offer a concurrent control for distinguishing treatment-related change from other influences.
Primary question
How did the mean VAS24 score change from baseline to Week 4 among participants in the defined full analysis set? The registry does not report the numerical answer.
3. Trial Design
The registry classifies this as a Phase 3, single-group study with no masking. Allocation is listed as not applicable, consistent with a design that has no randomized assignment between treatment groups. The study enrolled 219 participants and is marked completed. The recorded start was 2008-05 and primary completion was 2009-10. Janssen Pharmaceutical K.K. is listed as the sponsor.
All participants were assigned to the study intervention described in the record: tramadol hydrochloride plus acetaminophen (JNS013). There is no placebo or active-comparator arm in the listed design. That matters for interpretation: changes from baseline can be described, but a single-group design does not provide a contemporaneous control against which to compare those changes. It also cannot by itself separate change associated with treatment from change associated with time, expectations, measurement conditions, or other factors.
The registry title and summary describe a long-term efficacy and safety study, while the primary endpoint is specified at Week 4. The record also lists secondary outcomes involving pain measures and the Short Form-36. The timing and details of those outcomes should be interpreted from the registry descriptions rather than assumed to match the primary endpoint’s assessment schedule.
Details such as the planned statistical model, any sample-size justification, interim analyses, and the conduct of any additional control procedures are not reported in the registry record. The absence of a reported comparator does not establish what might have been considered during planning; it only describes the design recorded. The registry’s reported enrollment is not the same as the number in the primary analysis population or the safety population.
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: 219 participants were enrolled in this study out of which 29 participants did not meet the criteria to transfer to treatment period 1.
Overall Study
| Stage | Tramadol Hydrochloride Plus Acetaminophen (JNS013) |
|---|---|
| STARTED | 219 |
| Treated | 190 |
| COMPLETED | 97 |
| NOT COMPLETED | 122 |
Reasons for not completing this period:
| Reason | Tramadol Hydrochloride Plus Acetaminophen (JNS013) |
|---|---|
| Adverse Event | 43 |
| Withdrawal by Subject | 49 |
| violation of eligibility criteria | 2 |
| did not attend hospital appointments | 1 |
| not eligible for Treatment Period I | 22 |
| Physician Decision | 5 |
Analysis population for the primary outcome, as defined in the registry: Full analysis set included all participants who met the eligibility criteria, received study medication and had at least one post-treatment efiicacy assessment.
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 | Tramadol Hydrochloride Plus Acetaminophen (JNS013) |
|---|---|---|
| Participants analysed | 190 | |
| Age, Continuous | years | 64.3 (SD 12.9) |
| Sex: Female, Male: Female | Participants | 106 |
| Sex: Female, Male: Male | Participants | 84 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Visual Analogue Scale (VAS24) Score at Week 4, measured over Baseline and Week 4.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | millimeter |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the change from baseline in the Visual Analogue Scale score for pain over the last 24 hours, measured at Week 4. The registry describes the scale as running from 0 millimeter, meaning no pain, to 100 millimeter, meaning worst possible pain. A higher score at follow-up relative to baseline represents worsening, while a lower score represents improvement.
The endpoint is continuous: it records pain intensity along a graded scale rather than sorting participants only into broad categories. The registry specifies a mean as the summary measure and standard deviation as its measure of dispersion. In general, a mean summarizes the group’s average score, while a standard deviation describes how spread out individual scores are around that average. These summaries would help describe both the average change and the variability among participants.
The listed timeframe is baseline and Week 4, and the analysis population is the full analysis set. The registry does not report the baseline or Week 4 means, the mean change, the standard deviation, a confidence interval, or a test result. Consequently, the endpoint’s definition and direction can be explained, but the magnitude and precision of the observed change cannot be assessed from this record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies a clear primary measurement: change in the mean VAS24 score from baseline to Week 4. It also explains the scale’s direction, so a decrease would represent improvement and an increase would represent worsening. However, the record does not include the numerical primary outcome. It therefore supplies no observed mean change or standard deviation from which to describe the size or spread of the result.
No confidence interval or p-value for the primary endpoint is reported in the registry record. A confidence interval would ordinarily show the range of values compatible with the data under a specified method, while a p-value would address the data’s compatibility with a specified null hypothesis. Without those results, it is not possible to assess statistical precision or evidence against a null hypothesis. The record also does not report a statistical analysis for the primary outcome; the posted results include zero analyses.
The distinction between an endpoint definition and an endpoint result is important. A named measure tells the reader what the study intended to evaluate, not what participants’ scores did. Similarly, the registry’s description of the full analysis set explains who qualified for that analysis, but it does not give the number actually included or the number with usable baseline and Week 4 values.
The study’s single-group structure also limits what any change from baseline could establish. Even if a numerical change were available, it would describe change within the treated group. Without a concurrent comparator, the design does not provide a direct estimate of how outcomes would have differed under another treatment or under no study intervention. This is a design limitation, not a reason to disregard the measurement itself.
The accompanying tables and plots should be read alongside these reporting limits. The registry record does not provide the primary estimate or its uncertainty, so a display cannot be interpreted as a registry-reported treatment effect unless its underlying result is explicitly available elsewhere in the posted results. Planning illustrations are different again: they describe hypothetical sample sizes under stated assumptions, not observed efficacy or the probability that this trial detected an effect.
In short, the record supports a description of the research question, design, endpoint, and reported safety counts. It does not support a quantitative conclusion about the primary Week 4 change, its precision, or its statistical significance. The absence of a result in the registry record should not be replaced by an assumption about what the unreported analysis might have shown.
9. Statistical Methods Explained
The primary outcome is a continuous measurement summarized by a mean and standard deviation. In general, a mean gives the arithmetic average of the observed values, and a standard deviation describes how much individual observations vary around that average. The registry specifies that the measure is change from baseline, so the relevant outcome would summarize each participant’s Week 4 score in relation to that participant’s baseline score, followed by a group-level summary. The record does not state the statistical procedure used to estimate or test that change.
What does the scale measure?
The VAS24 records pain over the last 24 hours on a scale from 0 millimeter, no pain, to 100 millimeter, worst possible pain. As a continuous scale, it retains gradations in reported intensity rather than reducing responses to a small number of categories. The registry says that a decrease from baseline represents improvement and an increase represents disease progression. The score is a participant-reported measure; its interpretation depends on the reported experience and the measurement process. The registry does not report details about how assessments were administered or how the analysis handled unusual values.
What would a confidence interval add?
In general, a confidence interval communicates uncertainty around an estimated quantity. For a mean change, it would help readers judge how precisely the average change was estimated, in addition to seeing the estimate itself. A narrow interval generally indicates greater precision than a wide interval, given the analysis and assumptions used. No interval for the primary outcome is reported, and the record does not identify an interval-estimation method. It is therefore not possible to characterize the precision of the Week 4 estimate.
What would a hypothesis test add?
In general, a hypothesis test compares observed data with a stated null hypothesis using a specified statistical procedure. Its result depends on the test, its assumptions, and the data included. The registry does not report a primary-outcome test or p-value, and it does not specify the planned test. It would be inappropriate to infer a test result from the endpoint definition or from the fact that the study was Phase 3.
How should the analysis population be understood?
The full analysis set is defined as participants who met eligibility criteria, received study medication, and had at least one post-treatment efficacy assessment. This definition identifies a population for efficacy evaluation, but it does not state how many participants met all conditions. It also does not explain how participants without a Week 4 assessment were handled, whether other analysis populations were used, or whether any sensitivity analyses were planned. Those details are not reported in the registry record.
What do the planning illustrations represent?
In general, sample-size calculations depend on a target effect, variability, significance level, allocation, and statistical method. The planning illustrations accompanying this page use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They scale the effect to detect as a stated fraction of the observed effect. Those are planning assumptions for a hypothetical two-arm comparison, not a description of this single-group trial’s design. The illustrations are not observed power, do not establish that the trial was adequately powered, and do not substitute for a sample-size justification. The registry record does not report the trial’s own sample-size justification or the observed primary effect needed to interpret an effect-based planning illustration.
Why does design matter to the method?
A single-group baseline comparison is not the same as a randomized comparison between groups. A within-participant change can account for the fact that baseline and follow-up scores belong to the same participant, but the registry does not report whether a paired method or any other particular model was used. More generally, methods should match the data structure and the question. The record’s design and endpoint description do not reveal enough to reconstruct the analysis, and no analysis result is posted. Over-dispersion is a general concern for some count outcomes when variability exceeds what a simple count model assumes; it is not a reported feature of this continuous VAS endpoint, and no count model is specified.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome and secondary outcomes that include improvement from baseline in VAS24, pain intensity difference at Week 4, pain relief at Week 4, pain relief combined with pain intensity difference at Week 4, and change from baseline in Short Form-36 score. The record states that there are seven outcome measures, but the posted results do not include analyses. It does not report how many outcomes were tested, which outcomes were analyzed, or whether any outcomes were added or changed after study planning.
When several outcomes are examined, the chance of at least one apparently notable result can increase if each is tested separately. In general, a multiplicity strategy may define one primary test, adjust thresholds, or use another prespecified approach. The registry record does not report a multiplicity strategy, an adjustment method, or a hierarchy for interpreting secondary outcomes. No claim about whether multiplicity was controlled can be made from the outcome list alone.
The full analysis set definition requires eligibility, receipt of study medication, and at least one post-treatment efficacy assessment. The record does not report the number in this set, the number with Week 4 data, or the amount and pattern of missing outcome data. It also does not describe imputation, a complete-case approach, or sensitivity analyses for missing values. These methods can affect an estimate, so their absence limits assessment of how missing observations might influence the result.
The record does not report a sample-size justification, interim analyses, or the detailed statistical analysis plan. These matters are not recoverable from the endpoint labels alone. In particular, the posted results contain no analysis from which to judge whether the primary outcome was treated as the sole confirmatory 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 |
|---|---|---|---|
| Tramadol Hydrochloride Plus Acetaminophen (JNS013) | 24 | 190 | 12.6% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Tramadol Hydrochloride Plus Acetaminophen (JNS013) | 189 of 190 |
Most frequent serious adverse event terms
| Event term | Organ system | Tramadol Hydrochloride Plus Acetaminophen (JNS013) |
|---|---|---|
| Vomiting | Gastrointestinal disorders | 3 of 190 |
| Colon polyps | Gastrointestinal disorders | 2 of 190 |
| Nausea | Gastrointestinal disorders | 2 of 190 |
| Bronchitis | Infections and infestations | 1 of 190 |
| Gastroenteritis | Infections and infestations | 1 of 190 |
| Pyelonephritis | Infections and infestations | 1 of 190 |
| Cerebral infarction | Nervous system disorders | 1 of 190 |
| Diabetic autonomic nerve neuropathy | Nervous system disorders | 1 of 190 |
| Dizziness | Nervous system disorders | 1 of 190 |
| Loss of consciousness | Nervous system disorders | 1 of 190 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Tramadol Hydrochloride Plus Acetaminophen (JNS013) |
|---|---|---|
| Nausea | Gastrointestinal disorders | 101 of 190 |
| Constipation | Gastrointestinal disorders | 75 of 190 |
| Vomiting | Gastrointestinal disorders | 68 of 190 |
| Dizziness | Nervous system disorders | 52 of 190 |
| Nasopharyngitis | Infections and infestations | 49 of 190 |
| Somnolence | Nervous system disorders | 38 of 190 |
| Headache | Nervous system disorders | 28 of 190 |
| Weight decreased | Investigations | 23 of 190 |
| Gamma-glutamyltransferase increased | Investigations | 21 of 190 |
| Blood creatine phosphokinase increased | Investigations | 19 of 190 |
Serious events with the highest arm-level rate: vomiting (1.6%), colon polyps (1.1%), nausea (1.1%), bronchitis (0.5%), gastroenteritis (0.5%).
The safety summary lists 190 participants at risk for serious adverse events and 24 participants affected. It also lists 190 participants at risk for other adverse events and 189 participants affected. These are counts from the treatment group, not a comparison between separate treatment arms. The registry record does not report a death count; the death entry is not reported in the registry record.
The serious adverse event terms shown include vomiting, 1.6%; colon polyps, 1.1%; nausea, 1.1%; bronchitis, 0.5%; gastroenteritis, 0.5%; and pyelonephritis, 0.5%. These percentages are reproduced as listed. They describe the posted serious-event terms; they do not, by themselves, establish that the study intervention caused an event. The record does not provide a concurrent untreated or active-control group for comparison.
Participant counts and event terms are not interchangeable. A participant may have more than one event, and the listed affected-participant counts do not state the total number of event episodes. The registry summary also does not provide enough detail to assess timing, duration, severity beyond the serious-event classification, or the investigators’ attribution of events. Safety figures should therefore be read as descriptive reporting for the listed treatment group, not as a comparative risk estimate.
12. What the Result Does, and Does Not, Mean
This record establishes that a completed Phase 3 study evaluated long-term administration of tramadol hydrochloride plus acetaminophen in participants with chronic pain. It specifies the primary measure, its direction, the assessment at Week 4, and the definition of the full analysis set. It also presents descriptive safety counts and a list of serious adverse event terms.
It does not report the numerical primary outcome. Without the mean change and its variability, readers cannot judge the magnitude or consistency of change in VAS24 scores. Without a confidence interval, the precision of an estimate is unknown; without a reported test result and analysis method, statistical significance cannot be assessed. The registry record does not report a primary efficacy analysis.
The single-group design is another important boundary. A baseline-to-follow-up change in one treated group would not provide a randomized comparison with another treatment or a control condition. The record therefore cannot establish comparative efficacy from the listed design. Nor should the absence of a posted result be interpreted as evidence that there was no change or that a particular result was unfavorable; the numerical result is simply not reported in the registry record.
The safety summary is also descriptive. It reports affected participants and serious-event terms for the listed treatment group, but does not provide a control group with which to assess relative event frequency. The information is useful for understanding what was recorded, while remaining insufficient to attribute events to the intervention.
Planning illustrations should not be confused with what the trial observed. They are hypothetical calculations based on stated assumptions, not measured treatment effects, observed power, or proof that the study had adequate power. Overall, this record supports a careful account of the study’s purpose and structure, but not a conclusion about the size, precision, or comparative meaning of its primary efficacy result.
13. Why This Trial Matters Statistically
Statistically, this study is a useful example of why an endpoint description and a result are different kinds of information. The registry defines a continuous pain measure, identifies the direction of change, and specifies a Week 4 assessment. Those details make the intended question understandable. Yet the registry record does not post the mean change, its standard deviation, a confidence interval, or an analysis result. A well-defined measure cannot substitute for the missing estimate.
The design also makes the comparison question important. In a single-group study, participants receive the same listed intervention, so the central efficacy description would be change over time within that group. A change from baseline can be informative as a descriptive observation, but it is not the same as a contrast against a randomized control. That distinction helps prevent readers from treating a before-and-after result as a controlled treatment effect.
The record further illustrates the importance of analysis transparency. The full analysis set is defined, but its size and the handling of missing Week 4 assessments are not reported. The primary statistical method, multiplicity approach, interim analyses, and sample-size justification are also not reported in the registry record. Without these details and the result itself, readers cannot evaluate the analysis choices or the robustness of an estimate.
Finally, the safety figures show why denominators and event descriptions need to be read together. The listed counts describe participants affected within one treatment group; without a comparison group, they do not establish relative risks or causal attribution. The main statistical lesson is to keep the study’s question, design, analysis population, reported result, and limits of inference distinct.
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 interpretation is that the registry record does not report the numerical primary outcome or a statistical analysis. The mean change in VAS24, its standard deviation, a confidence interval, and a p-value are not reported. As a result, the magnitude and precision of the primary result cannot be evaluated from the record.
The single-group design offers no concurrent comparator. Any change from baseline, if reported, would describe change among participants receiving the listed intervention rather than a randomized between-group difference. This limits causal and comparative interpretation. The study is also unmasked, as recorded in the registry. For a participant-reported pain measure, the absence of masking is relevant context, though the registry does not report how expectations or measurement procedures were addressed.
The registry enrolled 219 participants, while its safety summary lists 190 participants at risk in the treatment group. These figures concern different reported aspects of the record; the registry excerpt does not explain the relation between them. The size of the full analysis set and the number with Week 4 outcome data are not reported. The handling of missing efficacy data and the details of the statistical model are also not reported.
Other design and reporting details that would inform interpretation—including a sample-size justification, interim analyses, and a multiplicity strategy—are not reported in the registry record. The listed safety counts do not provide a control-group comparison, and the death count is not reported in the registry record. These gaps mean that conclusions should remain limited to the study’s recorded design, endpoint definitions, and descriptive safety information.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Long-term Efficacy and Safety Study of Tramadol Hydrochloride Plus Acetaminophen (JNS013) in Japanese Participants With Chronic Pain — NCT00736957.
- Registry record last updated 2014-07-02; status last verified 2014-06.
- Results first posted 2013-06-20.
- 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
This completed Phase 3 study enrolled 219 Japanese participants with chronic pain and evaluated tramadol hydrochloride plus acetaminophen (JNS013). The registry lists a single-group, unmasked design with allocation not applicable. The recorded start was 2008-05, and primary completion was 2009-10.
The primary outcome was change from baseline in mean VAS24 score at Week 4, with lower scores representing improvement. The registry defines the full analysis set but does not report the numerical primary result or its statistical analysis. It lists secondary pain and Short Form-36 outcomes, and reports safety counts for 190 participants at risk. Serious adverse events affected 24 participants; the death count is not reported in the registry record.
The record supports description of the study question and design, but not a quantitative conclusion about the primary efficacy result or a controlled comparison.