The Analgesic Efficacy of Protocol for Primary Total Knee Arthroplasty (TKA): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Analgesic Efficacy of Protocol for Primary Total Knee Arthroplasty (TKA) (NCT03703206), a randomized phase 3 study. The primary outcome is Percentage of Patients Presenting With Pain in the Back of the Knee 6 Hours After Surgery.

2. Clinical Question

3. Trial Design

The registry identifies this as a phase 3, randomized, triple-masked, parallel-group study. Its brief summary describes allocation in a 1:1 ratio. The trial is listed as completed. The registry record gives enrollment as 120, with primary completion dated 2019-08-27 and study start dated 2018-07-01. Those dates describe the registered study timeline, not necessarily the timing of all data processing or reporting.

The two arms differ in whether iPACK is added to the adductor canal block. The ACB + iPACK arm is described as receiving an adductor canal block and an additional ultrasound-guided local anesthetic injection between the popliteal artery and the knee capsule. The ACB w/o iPACK arm is described as receiving the standard-of-care adductor canal block before total knee arthroplasty. Arm-level primary outcome results are listed for 60 and 59 participants, respectively. The registry does not explain the relationship between those outcome denominators and the enrollment figure.

Random assignment is intended to make the groups comparable on average, while masking is intended to limit influences from awareness of treatment assignment. The registry identifies triple masking but does not specify which people or roles were masked, or describe how masking was maintained. Details of sequence generation, concealment, block implementation, co-interventions, and deviations from assigned treatment are not reported in the registry record.

The primary endpoint concerns posterior knee pain six hours after surgery. Listed secondary outcomes include patient-reported pain scores and quality of recovery. A numerical secondary result is posted for pain score at 24 hours after surgery; a numerical quality-of-recovery result is not reported in the registry record. The record lists no reported analyses, so it does not establish which analysis populations, adjustment methods, or prespecified contrasts were used by the investigators.

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: 120 patients enrolled, 119 patients completed all necessary follow-up for inclusion in the study: 60 patients in the IPACK group and 59 patients in the sham group. There were no block failures. These 119 patients were randomized to receive either an IPACK or a sham block in addition to multimodal analgesia and an ACB. We were set to assess pain in the back of the knee 6 hours after surgery, quality of recovery after surgery, pain scores, opioid requirements, and functional measures

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 Percentage of Patients Presenting With Pain in the Back of the Knee 6 Hours After Surgery, measured over Six hours after surgery.

The primary endpoint is the percentage of patients reporting pain in the back of the knee six hours after surgery. The registry description says patients were to use a colored chart showing different knee regions, then indicate whether they had pain in a region. The regions included anterior, posterior, lateral, medial, and the middle of the thigh. The primary question focuses on the posterior region, with a yes-or-no response.

This endpoint represents a binary patient report summarized as a proportion. It is intended to capture the presence of pain at a specified location and time, rather than its intensity, duration, or effect on function. Reporting pain by location can distinguish posterior knee pain from pain elsewhere, which is relevant to the intervention’s stated analgesic question. The endpoint does not, on its own, describe the full pain experience or recovery.

The registry posts percentages for each arm, but does not provide the corresponding event counts, confidence intervals, or a formal comparison for this primary result. The endpoint description says all patients in the study would be in the denominator; the result entries do not further explain the denominator handling. Whether missing reports were counted, excluded, or treated in another way is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted results include two different kinds of outcome. The primary outcome is a proportion: whether a patient reported pain in a specified location at a specified time. The secondary pain-score outcome is summarized with means and standard deviations. These measures answer related but distinct questions, so their estimates should not be combined or treated as interchangeable.

What does the primary percentage represent?

A percentage for a binary endpoint describes the fraction of observations classified as having the event, expressed on a percentage scale. In this trial, the event is a report of pain in the back of the knee six hours after surgery. The percentages are 21.7% in ACB + iPACK and 45.8% in ACB w/o iPACK. A proportion can be clinically interpretable, but the percentage alone does not show the precision of the estimate. That requires information such as an uncertainty interval, which is not reported for this endpoint in the registry record.

In a two-arm comparison, the central statistical question is whether the observed difference is compatible with chance variation under a defined null hypothesis. Appropriate methods for binary outcomes depend on the event counts, denominators, analysis plan, and features such as missing outcome data. The record gives arm-level percentages and participant counts, but does not post event counts or a primary comparison estimate. No new difference or test can be inferred from those entries without conducting an analysis, which is not the role of a descriptive account of the registry results.

How should the secondary mean comparison be read?

The secondary pain-score result is a comparison of arm means at 24 hours after surgery. The posted means are 5.0 and 6.0, with a reported mean difference of 1.0 for ACB w/o iPACK relative to ACB + iPACK. The unadjusted p-value is p < 0.001. A mean difference expresses the separation between group averages on the recorded scale; it does not say how individual participants’ scores were distributed or how many experienced a particular degree of pain.

A confidence interval, in general, describes a range of estimates compatible with the data and the method’s assumptions. It conveys uncertainty around an estimate and is not a guarantee that the true effect lies within the interval. The posted secondary comparison includes an interval, but the registry’s exceptionally small standard deviations of 0.01 in both groups make the implied precision especially important to scrutinize. The record does not explain how those standard deviations were obtained or whether they reflect the intended score scale and data.

A p-value is a measure tied to a statistical model and null hypothesis. In general, it measures how unusual data at least as discrepant as those observed would be if the null model and its assumptions held. It is not the chance that the result occurred “by chance,” not the probability that treatment has no effect, and not a measure of clinical importance. The posted p-value is unadjusted, and the record does not describe a multiplicity plan.

Why do the assumptions matter?

Standard errors and confidence intervals depend on the variability in the data and the analysis method. For a mean comparison, smaller standard deviations imply greater precision, all else being equal. If variability is understated or recorded on an unexpected scale, the resulting interval and p-value may also overstate precision. The observed standard deviations of 0.01 are therefore a notable feature of the secondary entry, not a reason to assume that the estimate is definitive.

Over-dispersion is a general concern for count or binary data when variation exceeds what a chosen model expects. If present, standard errors based on a model that assumes less variation can be too small, making intervals too narrow and tests too favorable. The registry does not report an over-dispersion assessment for this endpoint, and the primary outcome’s posted information is not sufficient to evaluate one. This is a general methodological consideration, not a finding that over-dispersion occurred in this trial.

What do the planning figures mean?

The posted planning illustration uses the observed secondary mean difference as its basis. It assumes a two-sided significance level of 0.05, equal allocation, and a normal approximation, and considers planning for 100%, 75%, and 50% of the observed effect. Each illustration gives 1 participant per arm for 80% power and 1 participant per arm for 90% power. These are planning calculations, not observed trial results and not observed power. They are not evidence that the trial had a particular probability of detecting an effect.

Such calculations depend on the effect size and variability entered into the calculation. When the observed effect and reported standard deviations are used as inputs, the resulting planning figures can be highly sensitive to those inputs. They should not be read as a recommended sample size for a future study. A design-stage sample-size justification, including the investigators’ chosen target effect and assumptions, is not reported in the registry record.

For the primary binary outcome, no corresponding inferential calculation or planning illustration is reported in the registry record. The registry also does not describe an adjustment for baseline variables, a repeated-measures method, an analysis population, or a method for handling missing results. Consequently, the most defensible reading separates the primary arm percentages from the unadjusted secondary mean comparison, and treats both in light of the reporting gaps and the assumptions underlying each type of statistic.

10. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a multiplicity plan. It identifies a primary outcome and secondary outcomes, but does not state whether the investigators controlled the overall false-positive risk across these outcomes, used a hierarchy of tests, or regarded secondary analyses as exploratory. The posted secondary pain-score p-value is unadjusted. It should therefore be interpreted as a result for that comparison under its own calculation, not as a multiplicity-adjusted conclusion across the outcome set.

Missing-data handling is not reported in the registry record. The primary endpoint description says the denominator would include all patients in the study, but the result entries do not state how many patients posted a usable pain-location report, how incomplete reports were handled, or whether any participants were excluded from the calculation. The record also does not describe missingness for the secondary pain score or quality-of-recovery outcome. It is not possible to determine whether missingness could have affected the posted estimates.

The analysis population is also not reported in the registry record. There is no stated intention-to-treat, per-protocol, or other population definition, and no description of how randomized participants who did not receive the assigned procedure or lacked outcome data were treated. The arm counts attached to the primary results do not, by themselves, establish the analysis population or the number with complete outcome information.

These omissions matter because the reliability of an estimate depends not only on the arithmetic of the comparison but also on which observations were included and how outcomes were classified. Without a prespecified analysis description and missing-data account, readers cannot evaluate whether the reported results reflect all randomized participants or a subset selected by outcome availability or other post-randomization events. These details are not reported in 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 0% reporting threshold.

The posted safety entries list zero serious adverse events, zero other adverse events, and zero deaths in each arm. The corresponding at-risk counts are 60 for ACB + iPACK and 59 for ACB w/o iPACK. These are registry counts for the listed groups; they do not establish that adverse events were impossible or that no events occurred outside the categories or collection period represented by the record.

A zero count should be read as no events recorded in the specified category among the listed at-risk participants, not as proof of zero underlying risk. With no event counts above zero, the registry entries do not provide an estimate of the frequency of a particular adverse event, a comparative risk estimate, or an uncertainty interval. The record lists no top serious adverse-event terms.

The registry does not describe the safety surveillance period, event definitions, severity criteria, or whether ascertainment differed between groups. It also does not explain whether the reported counts cover all randomized participants or a defined safety population. Those details are not reported in the registry record, so the zero counts should be interpreted narrowly as the posted safety figures.

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

The primary result describes the percentages of participants in each arm recorded as reporting posterior knee pain six hours after surgery. The lower posted percentage in the ACB + iPACK arm is a descriptive difference between the registered arm results. Without a reported primary comparison and uncertainty interval, it does not establish how precisely that difference estimates a treatment effect or whether it could reflect sampling variation.

The secondary pain-score result points in the same descriptive direction, but it measures a different outcome at a later time. Its unadjusted p-value does not establish clinical importance, and the unusually small posted standard deviations raise questions about the precision implied by that comparison. A numerical quality-of-recovery result is not reported in the registry record, limiting the range of secondary information available.

The randomized, parallel design is relevant because randomization can support a fair comparison when the allocation process, follow-up, and analysis are conducted appropriately. The registry record does not provide enough detail to assess those elements fully. It identifies triple masking but does not identify who was masked or document implementation. It also does not report the analysis population, missing-data approach, multiplicity plan, or a formal primary analysis.

Accordingly, the posted results describe arm-specific pain outcomes and safety counts; they do not justify a broad conclusion about analgesic efficacy or safety. No medical recommendation follows from these registry entries. A more complete assessment would require a clearly reported primary comparison, its uncertainty, outcome denominators and event counts, and transparent information on analysis and missing data. Those details are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a registry result needs to be read at the level of the endpoint and the analysis actually reported. The primary outcome is a binary report of pain in a particular knee region at a particular time. Its arm-level percentages are easy to read descriptively, but the absence of event counts and an inferential comparison prevents assessment of precision from the registry entries alone.

It also illustrates why statistical significance in a secondary outcome does not settle the primary question. The secondary result concerns a pain score at another time point and is accompanied by an unadjusted p-value. The registry’s very small reported standard deviations make the apparent precision an important point for scrutiny. The result is not interchangeable with the primary endpoint, and it does not replace a prespecified primary analysis.

Randomization and masking are important design features, but their presence in a registry description does not answer every question about conduct or analysis. Readers still need to know how outcomes were collected, who was masked, what population was analyzed, how missing data were handled, and whether multiple outcomes were considered in the inferential plan. Those details affect how confidently results can be interpreted.

The posted planning illustration is another useful statistical distinction: calculations based on observed effects are not observed power and are not a substitute for a design-stage sample-size justification. Here, the planning inputs include the observed secondary effect and the registry’s reported variability, so the outputs should be treated as assumption-dependent illustrations, not as proof that a design is adequate.

For clinical researchers, the central lesson is that point estimates, uncertainty, design, and reporting completeness must be considered together. A directional pattern can be informative while still leaving substantial uncertainty about its magnitude and reliability.

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.

Several limitations are specific to the registry information available for this trial. The primary endpoint is reported only as arm-level percentages. Event counts, a formal comparison, and an uncertainty interval are not reported in the registry record, limiting the ability to assess the precision of the main result. The record does not explain the relationship between the endpoint denominator and the randomized or enrolled population.

The primary outcome is limited to a yes-or-no report of posterior knee pain at six hours after surgery. It does not measure pain intensity, later pain, pain in other locations as the primary endpoint, or functional recovery. A secondary pain score is listed at 24 hours after surgery, but it is a separate outcome at another time. A numerical result for the listed quality-of-recovery outcome is not reported in the registry record.

The secondary mean comparison is unadjusted, and the registry does not report a multiplicity plan. Its posted standard deviations are 0.01 in both groups, but no explanation of their calculation or data scale is given. The planning illustration based on that observed result is therefore sensitive to an input whose meaning cannot be assessed from the registry record. A protocol-based sample-size justification is not reported in the registry record.

Other relevant details are also absent: eligibility criteria, participant characteristics, intervention dose and procedural details, masking roles, co-interventions, outcome completeness, analysis populations, missing-data methods, and reported primary analyses. The safety entries give zero counts but do not describe the safety follow-up period or ascertainment procedures. These limitations concern the information in the registry record and do not establish that the underlying study lacked such methods or data.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Analgesic Efficacy of Protocol for Primary Total Knee Arthroplasty (TKA) — NCT03703206.
• Registry record last updated 2024-05-30; status last verified 2024-05.
• Results first posted 2024-05-30.
• 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

NCT03703206 is a completed phase 3 randomized, triple-masked, parallel-group trial of adding iPACK to an adductor canal block for primary total knee arthroplasty. The registry lists enrollment of 120 and describes a 1:1 allocation. The primary endpoint is the percentage reporting posterior knee pain six hours after surgery.

The posted primary percentages are 21.7% for ACB + iPACK and 45.8% for ACB w/o iPACK. No formal primary comparison or uncertainty interval is reported in the registry record. The secondary outcomes include patient-reported pain score and quality of recovery; a numerical quality-of-recovery result is not reported. The secondary pain-score comparison is unadjusted, and its reported standard deviations are 0.01 in both arms.

Safety entries list zero serious adverse events, zero other adverse events, and zero deaths in both arms. The registry does not report analysis populations, missing-data handling, or a multiplicity plan. The results are therefore best read as descriptive registry entries with important inferential and reporting limitations.