Persistent Postoperative Pain and Joint Stiffness After Total Knee Arthroplasty Performed for Osteoarthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Persistent Postoperative Pain and Joint Stiffness After Total Knee Arthroplasty Performed for Osteoarthritis (NCT02626533), a registered phase not stated study. The primary outcome is Presence of Persistent Postoperative Pain Using the Numeric Rating Scale (NRS).

2. Clinical Question

This is principally a question about the occurrence and potential predictors of postoperative symptoms, rather than a comparison of the effect of two assigned treatments. The listed follow-up assessments were intended to track pain over time, while blood and joint fluid samples could contribute biological measurements. The registry does not report which factors were associated with later pain or stiffness, or how those associations were assessed. It also does not report the number of participants meeting the primary pain definition at the specified follow-up. The stated aim is therefore broader than the primary endpoint alone, but the posted record does not provide findings that answer either the predictor question or the endpoint question.

3. Trial Design

The study enrolled patients undergoing total knee arthroplasty for osteoarthritis. The procedure is listed as the intervention, but no distinct comparison arm is described. Allocation is not stated, and the record does not describe a randomized treatment assignment. The study should therefore not be interpreted as a trial comparing arthroplasty with a control procedure or comparing alternative treatments. Its stated purpose was to examine clinical, biological, and psychological factors that may contribute to or predict persistent postoperative pain and joint stiffness.

Blood and joint fluid samples were to be obtained from patients. Pain type and severity were assessed at baseline, meaning enrollment, and at 4 weeks, 3 months, and 6 months after surgery. The primary endpoint concerns pain with activity in the operated joint at 6 months. Secondary outcomes include postoperative stiffness, knee range of motion, and pain scores at rest and with movement on postoperative days 1 and 2. The record lists 25 outcome measures in total, but does not give results for the primary endpoint or describe the findings for those secondary measures.

The registry records enrollment of 179 and a completed status. The listed study start is 2015-12, and primary completion is 2017-08-28. These dates describe the study record; they do not establish when each participant was assessed or whether every participant completed every assessment. Some patients were lost to follow-up, and the registry does not explain the timing or extent of that loss. The record also does not report eligibility details beyond the population description, the recruitment method, or a detailed analysis plan. These omissions limit what can be inferred about how representative the enrolled group was and how the follow-up data were handled.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Some patients lost to follow up

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 Presence of Persistent Postoperative Pain Using the Numeric Rating Scale (NRS), measured over 6 months after date of surgery.

The primary endpoint is the count of participants with persistent postoperative pain at 6 months after the date of surgery. Persistent pain is defined as an NRS score of at least 4 with activity in the operated joint. The stated scale runs from 0, no pain, to 10, worst pain imaginable; a lower score is described as a better outcome. The endpoint turns that pain assessment into a binary classification: a participant either meets the threshold or does not.

A thresholded endpoint can make a symptom measure easier to interpret as the frequency of participants meeting a prespecified definition. It also discards distinctions within each category. Participants with scores below the threshold may still have different pain experiences, and participants meeting the threshold may have different scores from one another. The binary count therefore does not describe the full distribution of pain intensity. The record does not report whether the underlying continuous NRS scores were also analyzed for the primary endpoint.

The endpoint is relevant to the study’s stated focus on persistent pain after surgery, and its timing places assessment at 6 months. However, the registry record does not report the observed count of participants meeting the definition, the number with usable endpoint data, or an estimate of uncertainty. The description notes that some patients were lost to follow-up. Without a reported result and a clear account of missing assessments, the endpoint definition alone cannot establish how common persistent pain was in the enrolled group.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is a binary outcome derived from a numeric pain rating. A participant is classified as having persistent postoperative pain if the activity-related NRS score in the operated joint reaches the stated threshold at the specified follow-up; otherwise the participant does not meet that endpoint definition. Counting participants in the positive category can communicate how many meet a clinical definition. To interpret a count as a proportion or risk, the number assessed must also be known and the denominator must correspond to the same outcome and follow-up. The registry record does not report the primary count or its assessed denominator.

Binary outcomes can be described with counts, proportions, risk differences, risk ratios, or odds ratios, depending on the question and analysis plan. These are general statistical options, not methods reported for this study. A count alone is not a comparison, and an association between a measured characteristic and the endpoint would require an analysis that accounts for how the characteristic and outcome were measured. The registry does not specify an effect measure or a model for examining potential predictors.

A confidence interval expresses the uncertainty around an estimated quantity under the assumptions of the analysis. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. Interval width is affected by factors such as the amount of usable information and the variability of the data. An interval is not a guarantee that the true value lies within it, and it does not address systematic errors such as selective follow-up or measurement bias. No confidence interval for the primary outcome is reported in the registry record.

For a continuous outcome such as an NRS score or knee range of motion, analysis could retain the numeric values rather than convert them into categories. Repeated measurements can also be analyzed to describe change over time or to account for the fact that assessments from the same participant are related. These are general approaches; the registry does not state whether continuous scores were analyzed, how repeated measurements were modeled, or whether the scheduled assessments were all included in an analysis. The primary endpoint itself uses a thresholded binary classification at 6 months.

Potential predictor analyses require particular care. A model may estimate associations between participant characteristics and an outcome, but its results depend on which predictors were selected, how variables were measured, how missing values were handled, and whether the model was specified before examining results. Predictive performance is also distinct from evidence that a characteristic causes an outcome. The registry record states an interest in clinical, biological, and psychological factors but does not report a prespecified predictor list, model-building process, validation method, or any resulting estimates.

What does over-dispersion mean?

In general, over-dispersion occurs when observed variability in count data is greater than a statistical model assumes. If ignored, standard errors can be too small, making intervals appear more precise than warranted and tests appear more conclusive. This concept is relevant to some count models, but the primary endpoint in this record is described as a count of participants meeting a binary definition, and the registry does not report a count model or an over-dispersion assessment. There is no basis to say that over-dispersion was present or that a particular method was used to address it.

What can be inferred from the planning assumptions?

The registry includes assumptions for a planning illustration: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those are planning assumptions, not evidence that the actual study used two randomized arms or followed that analysis plan. The registered study describes a single patient group and does not state an allocation method. Any sample-size figures generated under two-arm assumptions are therefore illustrations under those assumptions, not observed power and not a report of the study’s actual design justification. The registry does not report the study’s own sample-size justification, and no claim should be made that these illustrative assumptions were used to plan or analyze the study.

Multiplicity refers to the risk of obtaining apparently notable findings when many outcomes, time points, subgroups, or predictor tests are examined. General strategies include prespecifying a primary analysis or adjusting inference across a family of tests, but the appropriate approach depends on the scientific question. The record lists 25 outcome measures and does not report a multiplicity strategy. It is therefore not possible to determine whether the primary endpoint was protected from multiple testing or how secondary results should be interpreted as a group.

Finally, an analysis population is the set of participants whose data contribute to a particular result. In a longitudinal study, the available set can vary by outcome and visit. The record notes that some patients were lost to follow-up but does not describe which participants were included in the primary analysis or how missing assessments were treated. Such information is necessary to judge the denominator, potential selection effects, and the precision of a reported estimate.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 25 outcome measures, including the primary pain endpoint and secondary outcomes relating to stiffness, range of motion, and pain at several postoperative assessments. When many outcomes or time points are examined, the chance of finding at least one apparently notable result can increase. Statistical plans may address this through a prespecified hierarchy, adjustment, or a distinction between confirmatory and exploratory analyses. The registry does not report whether any such approach was planned or used. It is therefore not possible to assess how multiplicity was handled or to treat unreported secondary findings as confirmatory evidence.

Missing data are a central interpretive issue because the primary endpoint description says some patients were lost to follow-up. The registry does not give the number missing at the 6-month assessment, reasons for loss, or the timing of those losses. It also does not report whether missing outcomes were excluded, imputed, or addressed in a sensitivity analysis. Each approach relies on assumptions, and conclusions can depend on whether participants without follow-up differ systematically from those with observed outcomes.

The record does not identify the analysis population for the primary endpoint or for the secondary outcomes. Enrollment is recorded as 179, but that number should not automatically be taken as the denominator for every assessment. The serious adverse event data list a separate at-risk count of 162, and the record does not explain how that group relates to the enrollment total. No statistical analyses are listed in the registry record, so the handling of analysis populations, missingness, and multiple outcomes remains unreported.

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 serious adverse event record lists the group as total knee arthroplasty patients, with 162 participants at risk and 0 participants affected by serious adverse events. It also records 0 deaths. No serious event terms are listed. These figures describe what is entered in the registry’s serious adverse event fields; they do not establish that no event of any kind occurred, because the entries concern serious events and the record does not provide a complete account of non-serious events.

The at-risk count is not the same as the enrollment figure of 179. The registry does not explain the difference or state whether the safety group and the primary outcome population were defined in the same way. The 0 serious events should therefore be read with the recorded at-risk group in mind, rather than treated as a result for every enrolled participant. No causal comparison is possible because no separate control group is reported.

The record does not describe the safety monitoring procedures, event definitions beyond the serious-event category, duration of safety follow-up, or completeness of event collection. A zero entry is a registry finding, not proof that the procedure has no safety risks. The data support only a narrow statement: no serious adverse events or deaths are recorded for the listed group in these fields.

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

The record establishes that a study was conducted among patients undergoing total knee arthroplasty for osteoarthritis, with an aim of examining factors related to persistent pain and joint stiffness. It defines a primary pain endpoint at 6 months and describes repeated pain assessments and collection of blood and joint fluid samples. These details clarify the research question and the intended measurement framework.

The record does not report how many participants met the primary pain definition, how many had stiffness, or what the measured range of motion and pain scores were. It also does not report estimates linking clinical, biological, or psychological factors to later symptoms. As a result, the record cannot quantify the observed frequency of the primary outcome or identify predictors from the posted information. Stating these limits is different from concluding that symptoms were absent or that no associations existed.

The study is not described as a randomized comparison and has no separate control group listed. It therefore cannot provide a randomized estimate comparing the procedure with another treatment. The stated research purpose concerns identifying factors associated with or predictive of postoperative complications; even if associations were reported, association alone would not establish that a factor caused pain or stiffness.

The endpoint threshold is a practical classification, but it does not capture every difference in pain severity. A participant below the threshold can still report pain, and a participant meeting the threshold can have a range of scores. A binary result would answer whether the definition was met, not describe the entire symptom experience. Interpretation would also depend on how many participants posted data at the relevant follow-up and how missing observations were handled, neither of which is reported for the primary endpoint.

The serious adverse event entries record zero affected participants and zero deaths among the listed group at risk. They should not be expanded into a claim about all adverse events or interpreted as comparative evidence. Overall, the registry supports a description of study aims, follow-up, endpoint definitions, and the limited safety entries. It does not provide the outcome results needed to draw conclusions about the prevalence, predictors, or causes of persistent postoperative pain or stiffness.

13. Why This Trial Matters Statistically

This study’s statistical question is important because symptoms after surgery are not represented by a single measure. The record includes pain at rest and with movement, pain at different postoperative times, joint stiffness, and knee range of motion. It also describes collecting biological samples and considering psychological and clinical factors. This range of measures reflects the challenge of studying recovery: outcomes may differ in timing and type, and a single endpoint cannot describe every dimension.

The primary endpoint illustrates a common statistical choice: convert a symptom scale into a binary outcome using a threshold. Such a definition can make the result easier to communicate as the number of participants meeting a criterion, but it reduces information compared with retaining the original scale. The threshold, assessment time, and denominator all matter. For this study, the definition and timing are stated, but the registry does not report the number meeting the endpoint or the number assessed at that visit.

The study also highlights the difference between describing outcomes and identifying predictors. A predictor analysis requires documented measurements, a defined outcome, a prespecified or transparently reported modeling strategy, and attention to missing data and multiple testing. The registry states the intention to examine clinical, biological, and psychological factors, but does not post the analyses needed to evaluate that aim. Readers should distinguish the value of the research question from the evidence available in the record.

Finally, longitudinal follow-up and missing assessments affect interpretation. Enrollment does not necessarily equal the number contributing information at every visit, and the record acknowledges loss to follow-up without detailing its extent or handling. Clear reporting of endpoint counts, denominators, uncertainty, analysis populations, and missing-data methods is essential for judging how precisely results describe the participants and how far they may apply beyond them. In this record, those details are not reported, making transparent interpretation more important than inference from the study’s aims alone.

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 consequential limitation of the posted record is that it does not report the primary endpoint result. The definition is clear, but there is no count of participants with qualifying pain at 6 months, no corresponding assessed denominator, and no estimate of uncertainty. The registry also does not report results for the listed stiffness, range-of-motion, or early pain outcomes. Without those results, the study’s stated aims cannot be evaluated from this record.

The population description is limited to patients undergoing total knee arthroplasty for osteoarthritis. Eligibility criteria, recruitment details, and characteristics of enrolled participants are not reported in the available record. These omissions prevent assessment of how broadly the study population represents patients outside the enrolled group. The record notes that some participants were lost to follow-up but does not quantify that loss, explain its reasons, or state how missing observations were handled.

No separate comparison group or allocation method is described. This limits the study’s capacity, as registered, to support a treatment comparison or causal interpretation. The stated aim of identifying factors associated with or predictive of symptoms also requires analytic details that are not reported: there are no model descriptions, factor-specific results, uncertainty estimates, or validation details. The record does not state how multiple outcomes or analyses were addressed.

The safety information is similarly bounded. The listed serious adverse event group has 162 participants at risk, with 0 serious events and 0 deaths, but the record does not explain the relation of that group to the enrollment of 179 or describe non-serious events and safety follow-up in detail. These limits do not imply that the underlying study lacked such procedures or data; they mean those details are not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Persistent Postoperative Pain and Joint Stiffness After Total Knee Arthroplasty Performed for Osteoarthritis — NCT02626533.
• Registry record last updated 2024-12-27; status last verified 2024-02.
• Results first posted 2024-07-19.
• 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

The record describes a completed study of patients undergoing total knee arthroplasty for osteoarthritis, with enrollment of 179. Its aim was to identify clinical, biological, and psychological factors related to persistent postoperative pain and joint stiffness. Blood and joint fluid sampling and pain assessments at enrollment, 4 weeks, 3 months, and 6 months are described.

The primary endpoint is the count of participants with an activity-related NRS score of at least 4 in the operated joint at 6 months after surgery. Secondary outcomes include stiffness, range of motion, and pain measures during the early postoperative period. The study is not described as a randomized comparison, and no separate control group is listed.

The registry does not report the primary endpoint result, predictor analyses, or methods for handling missing data and multiplicity. It notes that some patients were lost to follow-up. The safety entry lists 162 participants at risk, 0 serious adverse events, and 0 deaths; no serious event terms are listed. The posted record therefore describes the research question and measurements but does not provide the outcome analyses needed to answer that question.