A Study of the Efficacy and Safety of EUFLEXXA™ for Treatment of Painful Osteoarthritis of the Knee: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Efficacy and Safety of EUFLEXXA™ for Treatment of Painful Osteoarthritis of the Knee (NCT00379236), a randomized na study. The primary outcome is Observed Pain Scores on 50-foot Walk Test During the Double-blind Study.

2. Clinical Question

The study also included an open-label safety extension. Participants from the double-blind study, including those initially assigned to placebo, could elect to enter it and receive EUFLEXXA™. This extension addressed safety after the masked comparison, but it does not preserve the same randomized placebo comparison for evaluating efficacy. The registry record lists several secondary measures, including pain on the walk test, WOMAC A pain, OARSI responders, patient global assessment, and rescue medication use. Numerical results for those measures are not reported in the registry record.

3. Trial Design

This was a multicenter, randomized, double-blind, parallel-group, placebo-controlled study of EUFLEXXA™ for painful knee osteoarthritis. The registry lists enrollment of 588 and describes the intended study size as approximately 600 subjects. The study status is completed. Its recorded start was 2006-10, and primary completion was 2007-12. The phase is listed as NA.

During the double-blind period, participants received either EUFLEXXA™ or placebo as three single-dose injections into the target knee, administered once weekly at weeks 0, 1 and 2. Follow-up continued for 26 weeks following the first injection. The randomized, masked placebo comparison is relevant because it helps separate differences between assigned groups from expectations and other influences that can affect assessments of pain. The record does not report the randomization method, allocation ratio, or details of how masking was maintained.

An open-label safety extension followed the double-blind study. Participants who had taken part in the 26-week study, including those assigned to placebo, could elect to participate. Those entering the extension received three EUFLEXXA™ injections. The recorded description specifies injections at weeks 26 and 27 but does not give the timing of the remaining injection. Since extension participation was elective and treatment was open label, extension observations should be read separately from the randomized comparison.

The registry lists 23 outcome measures and 8 analyses. It does not report a detailed statistical analysis plan, the planned primary comparison, or a sample-size justification for the original trial. The registry record also does not give numerical results for the primary endpoint.

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: A total of 821 patients were screened.

Double-blind

Reasons for not completing this period:

Open-label Extension

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to treat (ITT) population.

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 Observed Pain Scores on 50-foot Walk Test During the Double-blind Study, measured over Weeks 0, 26.

The primary endpoint was observed pain on a 50-foot walk test during the double-blind study. After walking 50 feet, each participant estimated their pain, with the investigator observing the assessment. Pain was recorded on a 100 millimeter visual analog scale: 0 millimeters represents no pain observed and 100 millimeters represents extreme pain observed. The registry identifies the measure as a mean with standard deviation and specifies weeks 0 and 26 as the timeframe.

A walking task gives the pain assessment a defined activity context rather than asking about pain without reference to movement. Pain during walking is relevant to the study’s focus on painful knee osteoarthritis, while the visual analog scale allows participants to express the perceived level of pain along a continuum. Comparing measurements across the randomized groups can describe how the recorded pain scores differed during follow-up. The registry identifies the intent-to-treat population for this primary outcome.

The endpoint description alone does not establish what the group scores were, how much they changed, or how uncertain the estimated comparison is. Those numerical results, including any confidence interval or test result, are not reported in the registry record. The endpoint therefore identifies what the investigators measured, but the registry information does not permit a quantitative conclusion about the comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical details available in the registry are limited. They identify a continuous primary measure, its summary as a mean with standard deviation, the assessment times, and the intent-to-treat population. They do not describe the full analysis procedure, the treatment contrast, the handling of repeated measurements, or the method used to account for missing observations. The concepts below explain how these methods are generally interpreted; they do not assert that any particular unreported method was used in this trial.

What does a mean with standard deviation describe?

For a continuous measure, a mean describes the average recorded score in a group. A standard deviation describes how spread out individual scores are around that group average. The mean can be useful for describing the group’s overall pain score, while the standard deviation gives context about variation between participants. Neither quantity by itself establishes a difference between randomized groups. A comparison requires an estimate of the contrast between groups, and interpretation of that estimate benefits from a measure of its uncertainty. The registry record does not report the primary endpoint’s group means or standard deviations.

Why does the randomized comparison matter?

Random assignment is generally used to make the treatment groups comparable, on average, with respect to factors that could influence outcomes. A placebo group provides a contemporaneous comparator, and masking can reduce the influence of expectations on assessments and reporting. These design features support interpretation of a between-group comparison, but they do not replace outcome data. The record does not describe the randomization procedure or allocation ratio, and it does not report the numerical primary comparison.

How should a confidence interval be understood?

In general, a confidence interval expresses the statistical uncertainty around an estimated effect. A narrower interval indicates greater precision under the assumptions of the analysis; a wider interval indicates less precision. The interval’s position relative to a relevant null value can also help readers understand which effects remain compatible with the data. The registry record does not report a confidence interval for the primary endpoint. No interval can be reconstructed from the information recorded because the necessary outcome summaries and comparison estimate are absent.

What can a p-value tell a reader?

In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the model assumptions held. It does not measure the size or clinical importance of an effect, and it does not give the probability that a treatment is effective. A p-value is most informative when read alongside the estimated effect and its uncertainty. The registry record does not report a primary-outcome p-value or enough numerical information to derive one.

What is the role of the planning illustration?

The sample-size assumptions describe a planning illustration based on a fraction of the observed effect. The stated framework uses a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. Such an illustration is a hypothetical planning calculation, not a description of the original trial’s design rationale and not evidence of observed power. It does not establish that the trial was designed using those assumptions. The registry record does not report the trial’s own sample-size justification. No numerical planning estimate or observed effect is reported in the information available for this interpretation.

Why can variability affect interpretation?

General statistical reasoning recognizes that a mean-based analysis is influenced by the spread of individual observations. Greater variability can make a group contrast less precise when other features are unchanged. If the distribution is more dispersed or irregular than a method assumes, standard errors and uncertainty estimates may be affected. These are general considerations, not findings about this trial: the registry does not describe over-dispersion or report diagnostic checks for the pain endpoint. Because the endpoint is continuous and summarized by a mean and standard deviation, those summaries would be relevant to understanding its distribution, but they are not reported.

The pain outcome was assessed at more than one specified time. Repeated measurements on the same participant are generally correlated, so an analysis of change or of multiple time points may need to account for that dependence. The registry record identifies weeks 0 and 26 but does not say whether the primary analysis compared scores at follow-up, analyzed change from baseline, or modeled measurements jointly. The outcome title refers to observed pain scores; no additional analytic interpretation should be inferred from the title alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 23 outcome measures and 8 analyses. When a study evaluates multiple outcomes, time points, or subgroups, the chance of obtaining at least one apparently notable result can increase if each analysis is interpreted without regard to the others. General approaches can include prespecifying a hierarchy, adjusting for multiple comparisons, or treating some findings as exploratory. The registry record does not report whether any such approach was planned or used. It also does not identify which secondary outcomes were confirmatory, how the analyses were prioritized, or whether outcomes were selected for reporting after results were known.

The primary endpoint is specified for weeks 0 and 26, but the record does not describe the statistical approach to those repeated observations. It does not state whether the primary contrast concerned follow-up scores, change from baseline, or another measure. Those distinctions matter because they define the quantity being estimated.

The primary outcome population is identified as intent to treat. In general, this label refers to analyzing participants according to their randomized assignment, regardless of treatment received, but it does not by itself explain how missing measurements are handled. The registry record does not report the amount or pattern of missing primary outcome data, the reasons for missingness, or any imputation or sensitivity analysis. It also does not specify the analysis populations for all secondary outcomes or the extension.

These omissions limit assessment of the robustness of any treatment estimate. Since the primary numerical results are not reported in the registry record, the effects of missing data or multiplicity on those results cannot be evaluated.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (0.7%), acute myocardial infarction (0.3%), arrhythmia (0.3%), salivary gland mass (0.3%), ankle fracture (0.3%).

In the double-blind period, serious adverse events were reported for 10 participants among 293 at risk in the EUFLEXXA™ group and 9 among 295 at risk in the placebo group. Other adverse events were reported for 27 among 293 at risk in the EUFLEXXA™ group and 35 among 295 at risk in the placebo group. These are counts with their recorded group denominators; no rates have been calculated.

For the open-label EUFLEXXA™ extension, the record lists 12 participants with serious adverse events among 433 at risk and 43 with other adverse events among 433 at risk. This is a selected, open-label group, not a randomized placebo comparison. Its counts should not be treated as directly comparable with those from the double-blind groups without considering the differences in study period and participation.

The registry lists pneumonia at 0.7%, and acute myocardial infarction, arrhythmia, salivary gland mass, ankle fracture, and lower limb fracture at 0.3% each among the top serious adverse event terms. These entries identify reported terms and percentages; they do not establish that an event was caused by study treatment. The registry does not report death counts in the safety fields. The listed counts alone do not describe severity beyond the serious-event classification, timing, or individual clinical circumstances.

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

The record establishes that a randomized, double-blind, placebo-controlled study evaluated EUFLEXXA™ in people with painful knee osteoarthritis. It identifies the primary measure as observed pain after a 50-foot walk, describes the scale, specifies the measurement times, and names the intent-to-treat population. These details clarify the intended question and the type of outcome collected.

They do not establish the magnitude or direction of the primary comparison. The registry record does not report the group scores, a between-group estimate, a confidence interval, or a p-value for the primary endpoint. Accordingly, the recorded information cannot show whether one group had higher or lower observed pain scores, nor how precisely any difference was estimated. A treatment effect should not be inferred from the study title, design, or endpoint description.

The safety counts provide descriptive information for the double-blind groups and the open-label extension. They do not by themselves establish a causal relationship between treatment and an event. The extension also differs from the randomized comparison because entry was elective and treatment was open label. Safety observations from that period therefore answer a different descriptive question.

The registry lists several secondary measures, but their numerical results are not reported in the registry record. Without those results, they cannot be used to support or challenge a conclusion about the primary endpoint. Likewise, the presence of an intent-to-treat label does not resolve questions about missing measurements or analysis choices that are not described.

The appropriate reading is therefore bounded: the design and measurement strategy are described, and some adverse-event counts are available, but the primary efficacy result and its precision are not. This is a limitation of the reported record, not evidence that the underlying study did or did not find a difference.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a randomized, masked, placebo-controlled design applied to a participant-reported pain measure in knee osteoarthritis. The walk test provides a defined activity context for the assessment, and the visual analog scale gives a continuous outcome that can be summarized with means and standard deviations. The placebo group and masking are important design features for interpreting subjective reports, because expectations can influence pain assessment.

The study also illustrates why a clear outcome definition is not enough for statistical interpretation. Knowing the scale, timing, and analysis population tells readers what was intended to be measured, but evaluating the comparison requires group results and an estimate of uncertainty. Those numerical primary results are not reported in the registry record. This distinction prevents design information from being mistaken for evidence about the observed treatment contrast.

The listed secondary outcomes show that the study assessed pain in more than one way, including responder definitions and other patient-reported measures. Multiple outcomes can provide complementary perspectives, but they also make prespecification and multiplicity handling important. The registry does not report whether or how multiplicity was addressed, limiting interpretation of any collection of secondary findings.

Finally, the open-label extension highlights the difference between randomized comparative follow-up and elective continued observation. The extension offers additional safety reporting, but its design does not preserve the original placebo comparison. Taken together, the record shows why design, outcome reporting, uncertainty, and analysis choices must be considered separately when reading clinical trial evidence.

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 important trial-specific limitation in the registry record is that numerical results for the primary pain endpoint are not reported. There are no group means or standard deviations, treatment contrast, confidence interval, or p-value in the record. The magnitude, direction, and precision of the primary comparison therefore cannot be assessed from this information.

The endpoint is specified at weeks 0 and 26, but the analysis of those measurements is not described. The record does not clarify whether the main comparison used follow-up scores, change from baseline, or another approach. It also does not report how repeated observations or missing measurements were handled. Although the primary population is identified as intent to treat, the label alone does not answer those questions.

The registry lists numerous outcomes and analyses but does not report a multiplicity strategy or distinguish confirmatory from exploratory analyses. Numerical results for the secondary outcomes are also not reported. This limits both assessment of the broader outcome pattern and evaluation of how selectively reported findings might affect interpretation.

The open-label extension was elective and followed the randomized period. The registry describes EUFLEXXA™ injections at weeks 26 and 27, but the timing of the third injection is not reported in the recorded arm description. Extension safety counts should be interpreted as descriptive observations from that distinct period, not as a continuation of the blinded placebo comparison.

Finally, details of the randomization procedure, allocation ratio, original sample-size justification, and full statistical analysis plan are not reported in the registry record. These gaps prevent a complete appraisal of the planned analysis and its relationship to the reported outcomes.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of the Efficacy and Safety of EUFLEXXA™ for Treatment of Painful Osteoarthritis of the Knee — NCT00379236.
• Registry record last updated 2011-12-28; status last verified 2011-12.
• Results first posted 2009-12-10.
• 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, multicenter, randomized, double-blind, parallel-group, placebo-controlled study of EUFLEXXA™ for painful knee osteoarthritis. Enrollment was 588. Participants received three weekly injections at weeks 0, 1 and 2, followed by 26 weeks of follow-up from the first injection. An elective open-label safety extension followed.

The primary endpoint was observed pain on a 50-foot walk test, measured on a 100 millimeter visual analog scale at weeks 0 and 26. The primary population was intent to treat, and the outcome was specified as a mean with standard deviation. Numerical primary results are not reported in the registry record. Safety counts are reported for the double-blind groups and extension, but they do not provide an efficacy estimate or establish causality.

The record does not describe the complete analysis plan, missing-data handling, or multiplicity approach. The primary treatment comparison and its precision therefore cannot be determined from the registry information.