Acetaminophen/Codeine vs Acetaminophen/Ibuprofen for Pain Control and Patient Satisfaction After Hand Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Acetaminophen/Codeine vs Acetaminophen/Ibuprofen for Pain Control and Patient Satisfaction After Hand Surgery (NCT02647788), a randomized phase 4 study. The primary outcome is Assessing Change in Pain Using the Visual Analogue Scale (VAS) Pain Score.

2. Clinical Question

The clinical question concerns pain after surgery, measured repeatedly while patients recovered at home and until their postoperative appointment. The record describes pain reports at dinner time, before sleep and in the middle of the night. The reported outcome was the average daily pain score, rather than one score at a single fixed time. The appointment was between 4 and 8 days after surgery.

The VAS runs from 0, meaning no pain, to 10, meaning the worst pain imaginable. Comparing these regimens therefore involves both the level of pain reported and the way pain scores change or vary across the postoperative period. The stated objective is equivalence, which asks whether the treatments differ by no more than a prespecified clinically acceptable margin. That margin is not reported in the registry record. A finding of no statistically significant difference alone would not establish equivalence.

The trial also listed Quality of Recovery-9 and number of pills used as secondary outcomes. Their results are not reported in the registry record. The available record therefore frames the clinical question, but does not provide the numerical evidence needed to determine the comparative pain outcome.

3. Trial Design

This was a Phase 4, randomized, double-blind, parallel-group pilot study at a single center. It compared two drug regimens in patients having ambulatory hand surgery. The record lists University of Pennsylvania as sponsor and gives the trial status as completed.

Random allocation is intended to make the treatment groups comparable, on average, with respect to both measured and unmeasured characteristics. Double masking means that two categories of people involved in the trial were intended to be unaware of assigned treatment; the registry record does not identify those categories or describe how masking was maintained. A parallel design assigns participants to a regimen and compares groups, rather than switching the same participants between regimens.

The registry lists enrollment of 144. It separately states that 111 patients completed the study and their data was included in the analysis. These are different record entries and should not be treated as interchangeable. Details about the reasons for non-completion, the number randomized to each group, and the analysis of participants who did not complete the study are not reported in the registry record.

The primary outcome was repeated pain reporting from after surgery until the postoperative appointment, described as occurring between 4 and 8 days after surgery. Participants reported pain three times each day, and the outcome description says the numbers reported are average daily pain scores. The record does not report how repeated daily scores were combined across days or specify one common assessment day for all participants.

The stated purpose was to assess whether the non-opioid combination would provide equivalent postoperative analgesia to the acetaminophen/codeine combination. Although that objective is stated, the registry record does not report an equivalence margin, a complete statistical analysis plan, or a single numerical primary-outcome comparison. These omissions limit what can be concluded from the design description alone.

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: There were 4 patients that were enrolled but did not make it to the randomization stage. 2 patients had liver disease and therefore met exclusion criteria for the study. The other 2 patients did not have surgery.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 111 patients completed the study and their data was included in the analysis

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.

Population: 144 patients were consented for this study. There were 4 patients that were enrolled but did not make it to the randomization stage and 140 patients were placed into the study. 111 patients completed the study and were included in analysis.

6. Primary Endpoint

The registry lists the primary outcome as Assessing Change in Pain Using the Visual Analogue Scale (VAS) Pain Score, measured over Subjects reported pain 3 times a day each day after hand surgery (at dinner time, before going to sleep and in the middle of the night), until post-op appointment (between 4 and 8 days after surgery). The numbers reported are the average daily pain scores.

The primary endpoint is change in pain assessed using the visual analogue scale (VAS). The scale is described as continuous, with 0 representing no pain and 10 representing the worst pain imaginable. A continuous score can preserve distinctions in reported pain across the scale, rather than reducing responses to categories such as pain present or absent.

Patients reported pain at three times each day: dinner time, before going to sleep and in the middle of the night. Reporting continued until the postoperative appointment, which took place between 4 and 8 days after surgery. The outcome description identifies the values as average daily pain scores. It does not specify a single day as the primary assessment or explain how daily scores were summarized across the full observation period.

Repeated reports can describe pain over the recovery period more fully than one isolated assessment. They also create an analysis issue: observations from the same person tend to be related, so treating every report as independent can misstate the uncertainty around a comparison. This is a general statistical consideration; the registry record does not report the method used to account for repeated measurements.

The outcome is recorded as a mean with standard deviation. A mean describes the average score, while a standard deviation describes how much individual scores vary around that average. Those summaries would help characterize pain levels and variability, but numerical primary-outcome results are not reported in a form that supports one comparison in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help interpret the design and the limits of the reported results. The registry record identifies a randomized parallel-group comparison and a continuous primary outcome summarized using a mean and standard deviation. It does not report the detailed statistical analysis used for the primary outcome. The explanations below describe general principles, not methods confirmed as having been used in this trial.

What does random allocation contribute?

In a randomized trial, assignment is determined by a chance-based process. Random allocation is intended to reduce systematic differences between groups at the start of the study. It does not guarantee that groups will be identical, especially in a pilot study, and it does not correct problems caused by missing outcomes or departures from the assigned treatment. The registry record gives the allocation as randomized but does not report the sequence-generation method, allocation concealment process or group-specific baseline characteristics.

In a parallel-group design, each participant is assigned to one regimen and outcomes are compared across groups. The comparison is usually interpreted as a difference between group summaries, but its meaning depends on how participants were analyzed and which observations were included. The record identifies the design as parallel and double-blind, but further procedural details are not reported in the registry record.

What do the mean and standard deviation describe?

For a continuous outcome, the mean is the arithmetic average of observed scores. The standard deviation describes the spread of scores around that average. The mean can provide an accessible summary of pain intensity, while the standard deviation helps show whether scores cluster closely or vary substantially among participants. Neither summary alone describes uncertainty in the difference between treatment groups. To assess that comparison, an effect estimate and an uncertainty measure, such as a confidence interval, are ordinarily useful.

A confidence interval is a statistical range constructed by a specified method. In general, it conveys the precision of an estimated effect: a narrower interval indicates less statistical uncertainty than a wider interval, though neither width nor location alone determines clinical importance. No primary comparison interval is reported in the registry record.

Why does repeated reporting matter?

Each participant reported pain several times per day, and reporting continued until the postoperative appointment. Repeated observations from the same participant are generally correlated: a person's report at one time may be more similar to that person's other reports than to another participant's report. General methods for repeated measurements account for this dependence. Treating all reports as if they came from unrelated people can make the analysis appear more precise than it is.

Repeated-measures methods can also use information about the timing and pattern of observations, but they require choices about the outcome model, correlation structure and missing reports. Alternatively, investigators may define a participant-level summary, such as an average over a prespecified period. The registry record says the numbers reported are average daily pain scores but does not state how scores were combined across days, how the repeated measurements were modeled, or how incomplete daily reports were handled. No particular method should be attributed to the trial on the basis of the record.

What is special about an equivalence objective?

Equivalence asks whether a treatment difference is sufficiently small to fall within a range considered acceptable for the clinical question. The acceptable range is set in advance as an equivalence margin. General equivalence analyses assess whether the uncertainty around the group difference excludes differences beyond that margin. A conventional test that fails to reject the hypothesis of no difference does not, by itself, show equivalence: a wide interval may still include differences that matter.

The trial description says its purpose was to establish whether the two regimens would provide equivalent postoperative analgesia. The registry record does not report an equivalence margin or a primary analysis result. Therefore, it is not possible to evaluate equivalence from the posted results. It is also not possible to infer that equivalence was the formal analysis approach merely from the stated objective.

How should the planning illustrations be understood?

Planning calculations are not observed trial outcomes and are not a measure of the trial's observed power. The record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also describes the effect to detect as a stated fraction of the observed effect. Such illustrations depend on those assumptions and are distinct from the number enrolled or the number whose data were analyzed.

For non-time-to-event outcomes, the stated convention is participants per arm for 80% power or another stated power level. The record describes time-to-event planning differently, as total events. These conventions do not establish what sample-size justification informed the original trial design. The trial's own sample-size justification is not reported in the registry record. In particular, an illustration computed from an observed effect should not be read as evidence that the trial was designed with that effect, or as observed power.

What can be inferred from a count of analyses?

The record lists zero analyses. This indicates that analysis results are not entered in the registry record; it does not show that investigators performed no analyses. It also means that the registry record does not document the specific model, hypothesis tests, adjustment strategy or sensitivity analyses. These details are important when interpreting a repeated-measures continuous endpoint and a stated equivalence objective. Without them, the methods cannot be reconstructed from the registry entry.

10. Multiplicity, Missing Data and Analysis Populations

The registry identifies three outcome measures, including the primary pain outcome and the secondary outcomes Quality of Recovery-9 and number of pills used. The primary outcome itself involves repeated reports across the postoperative period, and the registry indicates that it has several categories or time points rather than one reduced comparison. Multiple outcomes, time points or contrasts can create multiplicity: the more statistical questions examined, the greater the chance that some apparently notable result arises by chance. This is a general concern, not evidence that a particular adjustment was or was not applied in the trial.

A multiplicity strategy might specify one primary comparison, adjust for a defined family of tests, or identify secondary analyses as exploratory. The registry record does not report a multiplicity plan, a hierarchy of hypotheses beyond naming a primary outcome, or results that would permit review of such a strategy. It is not reported in the registry record whether interim analyses were conducted.

For missing data, the record states that 111 patients completed the study and their data was included in the analysis. It does not report the reasons for non-completion, the amount or pattern of missing pain reports, or the method used to handle missing data. It also does not identify an intention-to-treat population or describe a per-protocol analysis. The analysis population beyond the stated completed participants is not reported in the registry record.

Because pain was recorded repeatedly and follow-up ended at an appointment occurring between 4 and 8 days after surgery, missingness and observation timing could affect the available outcome data. General statistical approaches make different assumptions about why data are missing; the record does not state which assumptions or methods were used. Consequently, neither the effect of missing observations nor the robustness of the primary comparison can be evaluated from the registry record.

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 2.5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists adverse-event counts for each treatment group. For acetaminophen/ibuprofen, 0 serious adverse events are listed among 70 at risk, and 32 other adverse events are listed among 70 at risk. For acetaminophen/codeine, 0 serious adverse events are listed among 70 at risk, and 30 other adverse events are listed among 70 at risk. Deaths are listed as 0 in each group. No top serious adverse-event terms are listed.

These entries are counts, not a complete account of the nature, timing or severity of all events. The record does not report definitions for the serious and other categories, event-level details, attribution to study treatment, or whether participants could experience more than one event. Therefore, the other-event counts should not be read as counts of unique people unless the registry record establishes that interpretation; it does not.

A zero listed count means that the registry reports no events in that category for the listed group and denominator. It does not prove that the true risk is zero, and it does not establish a safety comparison between regimens. These safety figures are separate from the primary pain outcome and do not supply evidence about comparative analgesia.

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

The registry record describes a randomized, double-blind comparison of acetaminophen/ibuprofen and acetaminophen/codeine after ambulatory hand surgery. It specifies the primary measure, a VAS pain score summarized as an average daily score, and identifies secondary outcomes. It also reports that 111 patients completed the study and their data was included in the analysis. These details help define the question and the population contributing data as described in the record.

However, the record does not present a single numerical comparison of the primary outcome. Without group results or an effect estimate, it is not possible to state which group reported higher or lower average pain, how large any difference was, or how precise that comparison might be. The record likewise does not report numerical results for the named secondary outcomes.

The study's stated aim was to assess equivalence, but the registry record does not report an equivalence margin or the analysis needed to assess that aim. A lack of a reported difference is not evidence of equivalence, and the absence of a single primary comparison in the record should not be interpreted as evidence that the groups were the same. A proper equivalence conclusion requires both a clinically justified margin and sufficiently precise results.

The record also cannot establish whether any potential result would apply outside the study setting. It identifies the study as a single-center pilot and does not report further information needed to assess representativeness. The findings that can be described are therefore principally about the trial's design and recorded reporting, rather than a treatment effect.

The adverse-event counts offer a limited description of events entered in the registry, but they do not resolve the pain comparison or establish comparative safety. Overall, the posted information frames a relevant statistical question but does not include enough outcome detail to answer it quantitatively.

13. Why This Trial Matters Statistically

This trial raises several important statistical issues in a compact clinical setting. First, its stated objective is equivalence, not simply detection of a difference. Equivalence requires a defined margin and an analysis that establishes adequate precision around the treatment contrast. The registry record gives the objective but does not report the margin or a numerical primary comparison. This distinction matters because “no detected difference” and “evidence of equivalence” are not interchangeable conclusions.

Second, pain was measured repeatedly rather than at one single assessment. Repeated reporting can capture change during recovery, but measurements from the same participant are related. Appropriate analysis must account for that dependence or define a defensible participant-level summary. The record says the numbers reported are average daily pain scores but does not describe how measurements were combined across the full follow-up period.

Third, follow-up ended at an appointment occurring between 4 and 8 days after surgery. When observation periods vary, a clear analysis definition helps readers understand which days contribute to each participant's summary. The record does not report a common assessment day or the method for handling variation in follow-up timing.

Fourth, the record distinguishes enrollment from the completed participants included in the analysis. That distinction is important for understanding missing outcome data and the analysis population. Reasons for non-completion and methods for handling missing reports are not reported in the registry record.

Finally, the registry lists secondary outcomes and adverse-event counts, but these cannot replace a primary effect estimate with uncertainty. Together, these features show why transparent reporting of the estimand, repeated-measure method, missing-data approach, equivalence margin and confidence interval is central to interpreting a randomized trial. The record establishes the structure of the question but does not report those details sufficiently to quantify its primary result.

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.

This is described as a pilot study conducted at a single center. Those design features limit how broadly the trial's findings might be applied, although the registry record does not provide enough outcome results to assess the findings themselves. The enrollment entry is 144, while the record says 111 patients completed the study and their data was included in the analysis. Reasons for the difference and the handling of participants who did not complete the study are not reported in the registry record.

The primary outcome involved pain reports three times each day, with follow-up until an appointment between 4 and 8 days after surgery. The record describes average daily pain scores but does not explain how observations across days were combined, how variation in appointment timing was addressed, or how missing reports were handled. These details matter for interpreting a continuous, repeated outcome.

The primary objective was expressed as equivalence, but an equivalence margin and numerical primary comparison are not reported in the registry record. A single result cannot be evaluated for magnitude or precision from the information recorded. The registry lists zero analyses, which means the record does not include an analysis result; it does not establish whether analyses occurred outside the registry.

The masking details, randomization procedures, sample-size justification, multiplicity strategy, interim-analysis plan and statistical model are not reported in the registry record. Secondary-outcome results are also not reported. The adverse-event entries give counts but not event descriptions or treatment attribution. These reporting limits constrain assessment of the treatment contrast, the robustness of the analysis and the context of the safety counts.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Acetaminophen/Codeine vs Acetaminophen/Ibuprofen for Pain Control and Patient Satisfaction After Hand Surgery — NCT02647788.
• Registry record last updated 2019-02-18; status last verified 2019-02.
• Results first posted 2019-02-18.
• 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

NCT02647788 is a completed Phase 4, randomized, double-blind, parallel-group, single-center pilot study sponsored by University of Pennsylvania. It compared acetaminophen 650 mg with ibuprofen 400 mg against acetaminophen 300mg with codeine 30 mg for pain after ambulatory hand surgery.

The primary outcome was average daily pain on a VAS from 0 to 10, reported three times daily until the postoperative appointment between 4 and 8 days after surgery. The registry lists enrollment of 144 and states that 111 patients completed the study and their data was included in the analysis. Quality of Recovery-9 and number of pills used are named as secondary outcomes.

The registry record does not report a single numerical primary-outcome comparison, secondary-outcome results, an equivalence margin or the detailed statistical analysis. It lists 0 serious adverse events and 0 deaths in each group, along with other adverse-event counts of 32 and 30, respectively. The available record describes the trial but does not allow a quantitative conclusion about its primary comparison.