Three Injections of EUFLEXXA (Sodium Hyaluronate) for Treatment of Chronic Shoulder Pain Associated With Osteoarthritis (OA): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Three Injections of EUFLEXXA (Sodium Hyaluronate) for Treatment of Chronic Shoulder Pain Associated With Osteoarthritis (OA) (NCT00969501), a non-randomized na study. The primary outcome is Number of Participants With a Reduction in Pain by the Scores..

2. Clinical Question

The stated hypothesis is that three injections would be followed by improvement in pain levels and range of motion. The listed primary outcome addresses pain reduction; a measure of range of motion is not described among the posted outcome information. The central question that can be assessed from the registry record is therefore narrower than the full hypothesis: whether participants crossed the specified pain-reduction threshold by the stated follow-up.

Because there is no separate comparator group, the record cannot establish how outcomes under EUFLEXXA compare with outcomes under another treatment or with no treatment. A change from baseline can describe what happened to participants during the study, but it does not by itself isolate the effect of the intervention from other possible influences on pain scores.

3. Trial Design

This is an investigator-initiated exploratory case study listed as nonrandomized, unmasked, and single-group. The enrollment is 32, and the registry status is completed. EUFLEXXA is the listed intervention; the arm description labels it an active control, but the design fields identify only a single group. No separate control group or randomized allocation is described.

The registry record gives a start of 2009-08 and a primary completion of 2010-08. The primary outcome timeframe is 6 months. These dates and the stated timeframe describe the record's timeline; the registry record does not report participant-level follow-up completeness or whether every enrolled participant contributed data at the primary assessment.

Nonrandomized, single-group designs can describe outcomes observed in participants receiving an intervention. Without a concurrent comparison group, however, they do not provide a direct estimate of the difference between intervention and comparator outcomes. Lack of masking also means that participants and study personnel were not listed as masked. The registry record does not describe how outcome assessment was conducted or whether assessors were independent.

The record identifies the study as exploratory and lists phase as NA. It does not report a protocol-level statistical analysis plan, a sample-size justification, or any interim analysis. The listed enrollment should therefore be read as the number recorded for the study, not as evidence that the study was sized to detect a specified effect. Detailed eligibility criteria, recruitment methods, and participant baseline characteristics are not reported in the registry record.

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

Analysis population for the primary outcome, as defined in the registry: 

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 Number of Participants With a Reduction in Pain by the Scores., measured over 6 months.

The primary outcome is the number of participants with a reduction in pain by the scores, defined as a greater than 50 percent reduction in pain scores from baseline at 6 months. It is a binary responder outcome: each participant either meets the stated threshold or does not, assuming the required scores are available. The registry record names participants as the unit and describes the measure as a number, rather than reporting a mean change in pain score.

A threshold-based endpoint can make an outcome easier to interpret in terms of how many participants crossed a prespecified level of change. It also discards information about the size of changes within each category: participants just above the threshold and those with much larger reductions are both counted as responders. Participants just below it are classified differently despite potentially having similar changes. That is a general feature of dichotomizing a continuous measure, not a finding about this study.

The registry record does not identify the pain instrument, explain how scores were combined, or report the number who met the threshold. It also does not provide a result for range of motion, although improvement in range of motion appears in the stated hypothesis. Thus the endpoint definition is available, but its observed result and the measurement details needed to interpret it are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a binary primary outcome: participants are classified according to whether their pain scores fall by more than the specified threshold from baseline at 6 months. That outcome definition is not accompanied by a reported responder count or analysis. The following concepts explain how such results are generally interpreted; they do not describe analyses reported for this study.

What does a binary responder outcome represent?

A binary outcome groups observations into categories, such as meeting or not meeting a threshold. For a participant with a usable score, the registry's definition places the participant on one side of the greater-than-50-percent reduction threshold or the other. A group result would ordinarily report the count in each category and often the fraction of participants assessed who met the threshold. Neither the responder count nor the number assessed is reported in the registry record.

Thresholds can aid communication because the result can be expressed as the number of people meeting a defined criterion. However, categorization removes detail about the magnitude of each participant's change. A small difference around the threshold can change category, while substantial differences among people within the same category are not represented by the binary result. This is a general consequence of thresholding, not evidence about the observed participants in this study.

How should uncertainty be described?

In general, a confidence interval gives a range of values compatible with the observed data under the method used to construct it. For a responder outcome, an interval around a proportion can communicate uncertainty arising from the number of observations. Its width depends in part on the amount of information available and on the observed pattern of responses. A point estimate alone does not convey that uncertainty. The registry record lists no analysis and reports no interval for the primary outcome, so its precision cannot be assessed.

A statistical test, when appropriate, evaluates data against a stated null model and depends on the analysis plan and assumptions. A p-value is not a measure of the size or clinical importance of an effect, and it does not describe the probability that a treatment works. No p-value or hypothesis test for the primary endpoint is reported in the registry record. The absence of a reported test should not be interpreted as either evidence for or evidence against a difference.

What can a single-group analysis establish?

General statistical interpretation distinguishes a change over time within a group from a difference between groups. A single-group result can describe the recorded experience of participants assessed over time. It cannot, by itself, distinguish intervention-associated change from time trends, measurement effects, concurrent interventions, or other explanations. A comparator can help estimate a contrast, and random allocation can support comparability of groups, but neither feature is listed for this study.

Masking is another design feature that can affect how expectations influence reporting, care, or assessment. The registry lists no masking. It does not describe the outcome-assessment procedures, so the potential influence of knowledge of treatment assignment cannot be evaluated in more detail from this record.

How do the planning assumptions differ from the study design?

A planning illustration uses two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. It is described as based on the observed effect, with the effect to detect expressed as a stated fraction of that effect. These are planning assumptions, not evidence that the study itself used a two-arm design: the registry identifies this study as single-group. The numerical planning results and the effect value on which they are based are not reported in the registry record.

Such planning estimates describe hypothetical sample sizes for a chosen design and set of assumptions. They are not observed power, do not establish what the enrolled study could detect, and do not replace a report of the observed outcome with its uncertainty. Here, the registry record does not report the trial's own sample-size justification or a statistical analysis plan. Any planning calculation should therefore be kept separate from interpretation of the study's observed results.

Why does over-dispersion matter in some analyses?

In general, over-dispersion occurs when variability in data is greater than a statistical model assumes. If a model fails to account for that extra variability, its uncertainty estimates may be too narrow and tests may be poorly calibrated. This concern is relevant only when the data and model call for it; the registry record does not report a count model, an over-dispersion assessment, or an analysis for the primary outcome. It would be inappropriate to infer that such a method was used.

For this study, the main statistical limitation is more basic: the endpoint result and analysis are absent from the registry record. Methodological concepts can clarify what a complete report might contain, but they cannot supply the missing responder count, analysis population, or precision estimate.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("EUFLEXXA")
n      <- c(27)
events <- c(25)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  EUFLEXXA  27  25  92.6  75.7  99.1  76.6  97.9  76.5  97.7

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary outcome measure and no analyses. It does not report a statistical analysis plan or describe whether additional outcomes, time points, or subgroup comparisons were tested. Multiplicity refers generally to the increased chance of obtaining at least one apparently notable result when many statistical questions are examined. Whether and how that issue was addressed in this study is not reported in the registry record.

The stated hypothesis mentions pain and range of motion, while the listed primary outcome is a pain-responder count at 6 months. A range-of-motion result is not reported among the posted outcome information. The record does not explain whether that measure was collected, how outcomes were prioritized, or whether other analyses were planned. It is therefore not possible to assess the relationship between the stated hypothesis and the complete analysis program.

Missing-data methods and analysis populations are also not reported in the registry record. The enrollment of 32 does not establish that 32 participants had an outcome assessment at 6 months. The record does not state whether analyses were based on all enrolled participants, participants who completed follow-up, or another group; nor does it describe how missing pain scores were treated. For a binary endpoint, missing assessments can affect both the apparent responder count and the denominator used to describe it.

These omissions matter because the interpretation of a result depends on who contributed data, how incomplete observations were handled, and whether the analysis followed a prespecified plan. No particular approach should be assumed from the study design or endpoint definition. Those details are not reported in the registry record.

12. 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 0% reporting threshold.

The registry safety information lists the EUFLEXXA group with 32 participants at risk, 0 serious adverse events, and 0 other adverse events. These are recorded counts for the categories shown; the registry record does not provide event terms for either category. Deaths are not reported in the registry record.

A recorded count of 0 means that no events were entered for that category in the posted safety information. It does not prove that no events occurred outside the reporting system, that every participant had complete safety follow-up, or that an event could not occur. Interpreting a zero count also depends on how events were defined, collected, and attributed. Those procedures are not reported in the registry record.

The counts do not include a reported uncertainty interval or a comparison with another group. Since the study is listed as single-group, these data cannot show a comparative difference in safety outcomes. The count of participants at risk should not be confused with a reported count of participants completing the entire study or contributing every assessment. Follow-up completeness and the safety-analysis population are not reported in the registry record.

These figures should therefore be read narrowly as the adverse-event counts entered for the listed group, rather than as a comprehensive estimate of risk or evidence about comparative safety.

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

The registry record documents an exploratory, single-group study of three EUFLEXXA injections for chronic shoulder pain associated with osteoarthritis. It specifies a primary pain endpoint: the number of participants with a greater than 50 percent reduction in pain scores from baseline at 6 months. This makes the intended outcome question clear, but the registry record does not report the number who met the threshold.

Without that result, the posted information cannot show the observed frequency of response or how precisely it was estimated. It also cannot establish whether pain scores changed, by how much they changed, or whether range of motion improved. A stated hypothesis describes what investigators expected to examine; it is not an observed finding.

Even if a within-group change were reported, the single-group nonrandomized design would not provide a direct comparison with an alternative. Changes could reflect the intervention, natural variation over time, other care, expectations, or measurement processes. The absence of masking is another feature relevant to interpreting subjective pain scores. The registry record does not give enough information to assess the contribution of these influences.

The recorded safety information lists 0 serious adverse events and 0 other adverse events among 32 at risk, with deaths not reported in the registry record. These counts describe the entries in the safety record, not every possible event or the risk relative to another treatment. Follow-up and event-collection details are not reported.

The appropriate reading is therefore limited: the record defines a clinical question and reports basic design and safety information, but it does not provide the primary outcome finding or an analysis of it. It supports no conclusion about the magnitude, precision, or comparative nature of changes in pain or range of motion.

14. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported endpoint result are both necessary for statistical interpretation. The registry identifies a responder threshold for pain at 6 months, allowing readers to understand what investigators intended to count. But without the responder count, the number assessed, and an estimate of uncertainty, the endpoint cannot be evaluated as an observed result.

It also highlights the distinction between describing outcomes and estimating comparative effects. A nonrandomized, single-group design can organize observations around an intervention, but it has no concurrent comparator in the listed design. A within-group change, even if reported, would not by itself separate the intervention's contribution from other explanations for change. This distinction is central when interpreting exploratory case studies.

The registry's arm description labels EUFLEXXA an active control, while its design fields specify a single group. Reading design information together helps avoid assuming a comparison that is not described. The planning assumptions likewise refer to equal allocation between two arms, whereas the study itself is listed as single-group. Planning illustrations and actual trial designs answer different questions and should not be conflated.

Finally, the record demonstrates that an endpoint definition, completed status, and safety counts do not substitute for a statistical results report. Analysis populations, missing-data methods, precision estimates, and a statistical plan are not reported. Recognizing those gaps is part of statistical appraisal: it limits conclusions to what the record documents rather than encouraging readers to infer unreported findings.

15. 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 primary limitation for interpreting this specific study is that the registry record defines the primary outcome but does not report its observed value. The number of participants with a greater than 50 percent reduction in pain scores at 6 months is not reported in the registry record. No analysis is listed, and no uncertainty estimate is available for the endpoint.

The study is described as nonrandomized and single-group, with no masking. A separate comparator is not identified, so the record cannot support a direct treatment contrast. The lack of masking is relevant to a pain-score outcome, but the registry record does not describe how scores were collected or assessed. It is also not reported whether range of motion was measured or analyzed, despite its mention in the stated hypothesis.

Although enrollment is 32, the number assessed at the primary timeframe and the analysis population are not reported in the registry record. The handling of missing data, withdrawals, and incomplete follow-up is also not reported. The pain instrument, dose details, eligibility criteria, baseline characteristics, and other care received are not reported in the registry record, limiting assessment of measurement and applicability.

The registry record does not report a statistical analysis plan, sample-size justification, interim analyses, or methods for handling multiple outcomes. The listed adverse-event counts lack accompanying event terms and details of collection or follow-up; deaths are not reported. These limitations concern what can be learned from the registry record and do not establish that unreported procedures or measurements did not occur.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Three Injections of EUFLEXXA (Sodium Hyaluronate) for Treatment of Chronic Shoulder Pain Associated With Osteoarthritis (OA) — NCT00969501.
• Registry record last updated 2013-05-07; status last verified 2013-03.
• Results first posted 2013-05-07.
• 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.

19. Record Summary

The registry record describes a completed, investigator-initiated exploratory case study of EUFLEXXA for chronic shoulder pain associated with osteoarthritis. It lists a nonrandomized, unmasked, single-group design and enrollment of 32. The stated intervention is three injections, and the primary outcome is the number of participants with a greater than 50 percent reduction in pain scores from baseline at 6 months.

The record does not report the primary outcome count, a statistical analysis, or the precision of an estimate. It also does not report the analysis population, missing-data methods, or a statistical plan. The safety information lists 0 serious and 0 other adverse events among 32 at risk; deaths are not reported in the registry record. The available information defines the question and records basic design details, but does not provide the clinical outcome result needed to assess the study's stated hypothesis.