This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Optimization of Synvisc-One for Knee OA (NCT02029703), a randomized na study. The primary outcome is Difference in Pain Score Between Groups.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02029703 |
| Phase | NA |
| Condition | Knee Osteoarthritis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 42 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Elaine Husni |
| Results posted | Yes |
2. Clinical Question
Population
People diagnosed with primary knee osteoarthritis who required physical therapy. The registry record gives no further eligibility details or description of the analysis population.
Intervention
A single Synvisc-One injection alongside standardized physical therapy. The arm description specifies a 6 mL intra-articular injection.
Comparator
A sham injection alongside standardized physical therapy. The registry describes the sham as lidocaine 1% at 1-2 ml; the full procedural description is not reported in the registry record.
Primary question
What is the between-group difference in KOOS pain subscale scores at 12 and 24 weeks? The registry describes the outcome as a mean score on a 0-100 scale, with higher scores indicating better status. Numerical outcome results are not reported in the registry record.
The trial's stated hypothesis was that Synvisc-One would improve physical therapy compliance and performance and thereby improve knee function and pain compared with sham injection, with both groups receiving a standardized physical therapy regimen. That is the rationale recorded for the comparison, not a finding. The primary objective narrows the outcome question to the KOOS pain subscale and between-group score differences over the stated follow-up timepoints.
The registry record lists 42 enrolled participants and identifies the study as randomized, double masked, and parallel group. It does not describe who was masked, the randomization procedure, or how compliance and physical therapy performance were measured. The treatment descriptions identify the assigned injections, but the record does not establish how similar participants perceived the procedures to be.
Because no group means, between-group estimates, confidence intervals, or hypothesis-test results are reported for the primary outcome, the treatment contrast cannot be quantified from the registry record. The stated clinical question can be identified, but its answer cannot be determined from the posted results.
3. Trial Design
This was a randomized, double-masked, parallel-group trial listed as phase NA. The registry record identifies knee osteoarthritis as the condition and records enrollment of 42. It lists Synvisc-One injection and sham injection as the interventions. The comparison was intended to assess Synvisc-One as an adjunct to standardized physical therapy, with standardized physical therapy also used in the sham group.
The Synvisc-One arm description specifies a single 6 mL intra-articular injection. The sham arm description specifies lidocaine 1% at 1-2 ml and a sham procedure. The procedural descriptions in the registry record are incomplete, so further details should not be inferred. The Synvisc-One arm description also notes an unblinded treating physician. The record labels the study double masked but does not say which other people were masked or how masking was maintained.
The brief summary describes the physical therapy regimen as lasting 10 weeks. The primary outcome timeframe, however, is stated as 12 and 24 weeks. The record does not explain the relationship between the physical therapy period and those assessment timepoints, or give the exact schedule of assessments.
The study status is terminated. The registry record lists a start of 2012-08 and primary completion of 2015-11, but does not report why the trial was terminated or whether the planned follow-up and assessments were completed. The outcome record identifies one primary measure, but no analysis results are listed. The planned sample-size justification, randomization details, allocation concealment, and statistical analysis plan 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
| Stage | Sham Injection | Synvisc-One Injection |
|---|---|---|
| STARTED | 20 | 22 |
| COMPLETED | 20 | 22 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Sham Injection | Synvisc-One Injection | Total |
|---|---|---|---|---|
| Participants analysed | 20 | 22 | 42 | |
| Age, Continuous | years | 61.2 (SD 13.4) | 59.2 (SD 10.2) | 60.1 (SD 11.7) |
| Sex: Female, Male: Female | Participants | 14 | 17 | 31 |
| Sex: Female, Male: Male | Participants | 6 | 5 | 11 |
| Number of Participants | Participants | 20 | 22 | 42 |
6. Primary Endpoint
The registry lists the primary outcome as Difference in Pain Score Between Groups, measured over 12 and 24 weeks.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the between-group difference in the KOOS pain subscale score at 12 and 24 weeks. KOOS is the Knee injury and Osteoarthritis Outcome Score; its pain subscale is intended to measure pain-related status in people with knee problems. The registry describes the score as ranging from 0 to 100, with higher scores indicating better status. It describes the endpoint as a mean of a continuous measure, with standard deviation as its dispersion measure.
A continuous score retains differences across the scale rather than sorting participants only into categories. A group mean can describe the average score, while a between-group contrast expresses how the group averages differ. A standard deviation describes variation among individual scores within a group; it does not by itself quantify the precision of the estimated group difference. For that, an uncertainty measure such as a confidence interval would be useful.
In general, using a pain subscale makes the outcome directly relevant to the trial's stated pain question, while the common score scale allows comparison between the randomized groups. The registry record does not report a threshold for a clinically important score difference, and it does not state how missing responses or repeated measurements were handled. Most importantly, it contains no numerical group scores or estimated contrasts. The endpoint and its direction can therefore be described, but the size and precision of any observed difference cannot be assessed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the intended primary comparison: mean KOOS pain subscale scores in the Synvisc-One and sham-injection groups at 12 and 24 weeks. It gives the scale range and direction, but does not report group means, standard deviations, between-group differences, confidence intervals, or p-values. The primary outcome therefore has no numerical result in the posted record that can be interpreted as an estimate of the treatment contrast.
The trial is listed as terminated, and the record reports enrollment of 42. Neither fact establishes what the outcome results were. Termination alone does not indicate whether results were favorable, unfavorable, inconclusive, or unavailable for another reason; the reason for termination is not reported in the registry record. Enrollment does not show how many participants contributed data at each timepoint, and those analysis counts are not reported.
The scale direction is important when interpreting a result if one is available: a higher KOOS pain score represents better status. But direction alone cannot establish the direction or magnitude of a between-group effect. No conclusion about the observed pain-score contrast can be drawn without the group-level outcome data or an estimated difference. Nor can precision be assessed without an uncertainty interval or another measure of estimate uncertainty.
In general, a confidence interval describes a range of values compatible with the data and the statistical model, and it helps distinguish a relatively precise estimate from one with substantial uncertainty. A p-value, if reported, would address compatibility with a specified null hypothesis under the analysis assumptions; it would not by itself give the effect's size or clinical importance. Neither type of result is reported for the primary endpoint in the registry record.
The registry lists serious and other adverse-event counts, which are separate from the primary pain outcome. These counts do not supply evidence about the endpoint, physical therapy compliance, or knee function. The record does not provide an analysis connecting safety events to treatment effects, nor does it report outcome results for compliance or performance. The stated hypothesis should thus be read as the rationale for the trial, not as an observed result.
Overall, the posted results support a description of the study question and design, but not an estimate of the intervention's effect on pain. They also do not allow assessment of whether the study had enough information to distinguish a meaningful effect from chance variation. This is a limitation of what is reported in the registry record, rather than evidence for either direction of the treatment effect.
9. Statistical Methods Explained
The endpoint is continuous: it is described as a mean KOOS pain score, with standard deviation used to characterize dispersion. The assigned groups are compared on that outcome. This description identifies the general form of the planned measurement, but the registry record does not report the statistical model or the exact estimator used for the comparison.
In general, a mean summarizes the center of a set of numerical observations. A standard deviation describes how spread out those observations are around their mean. These answer different questions: the mean is about the average score, while the standard deviation describes participant-level variability. A standard deviation is not a confidence interval and does not directly show how precisely the group difference has been estimated.
For a comparison of two group means, an analysis may estimate a difference and its uncertainty. A confidence interval is useful because it communicates both the direction and the range of effect sizes compatible with the data and the analysis assumptions. A hypothesis test may also produce a p-value, but a p-value is not the probability that a treatment effect is true, and it does not measure clinical importance. The registry record reports none of these primary-outcome statistics, so no trial-specific effect estimate or uncertainty can be discussed.
The primary timeframe names 12 and 24 weeks. Repeated measurements on the same participant are generally statistically related; an analysis may need to account for this dependence if it models both timepoints together. Alternatively, a trial may define separate contrasts at each timepoint or use another prespecified approach. The registry record does not say which approach was planned or used, whether one timepoint had priority, or whether results were adjusted for baseline scores. No method should be attributed to the trial without that information.
In general, randomization aims to make the assigned groups comparable at the start of a trial, on average, with respect to factors that could affect the outcome. It does not guarantee identical groups in a small study. The registry describes the study as randomized but does not report the sequence-generation method, allocation concealment, or baseline characteristics. Consequently, the quality and implementation of these design protections cannot be evaluated from this record.
The record labels the trial double masked, but does not identify the masked roles. It also describes an unblinded treating physician in the Synvisc-One arm. These registry entries do not establish whether participants, outcome assessors, or analysts remained unaware of assignment. In general, masking can reduce the influence of expectations on participant reports, care, and outcome assessment, but its effectiveness depends on how it is implemented. The registry record does not report whether masking was assessed or maintained.
The study is described as parallel group, meaning that participants are assigned to a group rather than crossing between intervention conditions. The listed intervention and comparator both accompany standardized physical therapy, making the intended contrast the addition of Synvisc-One versus the sham injection in that setting. The record does not report whether physical therapy attendance, compliance, or performance was measured, despite naming those concepts in the study hypothesis.
The sample-size assumptions recorded for a planning illustration are a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. They describe an illustration based on the observed effect and fractions of that effect; they are not the trial's own design justification. The registry record does not report the trial's original sample-size calculation or its target power. Any sample-size illustration is a planning aid, not observed power and not a substitute for an outcome estimate.
In general, over-dispersion occurs when variability in the data is greater than assumed by a statistical model. If a model underestimates variability, uncertainty intervals may be too narrow and tests may be misleading. This concept is particularly relevant to models for counts or rates; the primary measure in this trial is a continuous score, and the registry record does not report a model or evidence of over-dispersion. It would therefore be inappropriate to claim that over-dispersion was present or that a correction was used.
The registry marks the primary outcome as involving several timepoints and does not reduce it to one comparison. When several outcomes or timepoints are tested, multiplicity can raise the chance of at least one false-positive result if each is treated as an independent confirmatory test. In general, a protocol may address this by specifying a primary contrast, an adjustment, or a hierarchy of tests. The record does not report such a strategy or any analysis results, so multiplicity control cannot be evaluated.
There are no listed analyses for the primary outcome in the registry record. The record also does not state whether analyses followed intention-to-treat principles, which participants were included in each analysis, how missing scores were handled, or whether sensitivity analyses were conducted. These omissions prevent evaluation of the analysis population, attrition, model assumptions, and robustness. They do not establish that a particular method was or was not used outside the information recorded in the registry.
10. Multiplicity, Missing Data and Analysis Populations
The primary outcome is described across 12 and 24 weeks, and the registry notes that the outcome has several categories or timepoints and was not reduced to one comparison. This matters because interpreting several tests as though each were the sole primary test can increase the chance of a false-positive finding. In general, a prespecified testing hierarchy or a suitable adjustment can address multiplicity, but the registry record does not report whether either was planned or used. No primary-outcome analyses are listed.
Missing outcome data can also affect interpretation. If participants with unobserved scores differ systematically from those with observed scores, an analysis restricted to available measurements may not represent the originally randomized groups. In general, statistical approaches can make different assumptions about why values are missing; sensitivity analyses can examine how conclusions change under alternative assumptions. The registry record does not report missing-score counts, reasons for missingness, imputation methods, or sensitivity analyses.
The analysis population is not specified. The record does not say whether the primary analysis was intended to include all randomized participants, only those who received treatment, or another group. It also does not report the number contributing scores at either follow-up timepoint. These details are needed to assess how the randomized comparison was preserved and how much outcome information was available.
The record lists one outcome measure and zero analyses. This means the registry record does not provide an analytical result to assess; it does not establish which analyses may have been conducted elsewhere. The statistical analysis plan, any interim analyses, and the handling of multiple timepoints are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Sham Injection | 0 | 20 | 0.0% |
| Synvisc-One Injection | 1 | 22 | 4.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Sham Injection | 0 of 0 |
| Synvisc-One Injection | 0 of 0 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Sham Injection | 3 of 20 |
| Synvisc-One Injection | 2 of 22 |
Most frequent serious adverse event terms
| Event term | Organ system | Sham Injection | Synvisc-One Injection |
|---|---|---|---|
| Depression Requiring Hospitalization | Psychiatric disorders | 0 of 20 | 1 of 22 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Sham Injection | Synvisc-One Injection |
|---|---|---|---|
| Worsening Knee Pain | Musculoskeletal and connective tissue disorders | 3 of 20 | 2 of 22 |
Serious events with the highest arm-level rate: depression requiring hospitalization (4.5%).
The registry record reports serious adverse events for the two groups separately. In the sham-injection group, 0 of 20 participants at risk were reported as affected by a serious adverse event; in the Synvisc-One group, 1 of 22 participants at risk was reported as affected. Deaths were reported as 0 in each group. These are event counts in the registry record, not estimates of comparative risk adjusted for follow-up or other factors.
For other adverse events, the record reports 3 of 20 participants at risk in the sham-injection group and 2 of 22 in the Synvisc-One group as affected. The registry also lists Depression Requiring Hospitalization at 4.5% among its top serious terms. The record does not explain the denominator or provide enough context to interpret that percentage alongside the group counts.
In general, adverse-event counts require context, including how events were defined, how long participants were followed, whether multiple events in one participant were counted, and how completely events were collected. These details are not reported in the registry record. The counts alone do not establish a causal relationship to an injection and should not be treated as a complete safety comparison. They are also distinct from the unreported primary pain-score results.
12. What the Result Does, and Does Not, Mean
The registry record establishes the trial's intended question and gives some design and safety information. It does not report the numerical primary outcome results. Therefore, it cannot show the size or direction of the difference in KOOS pain scores between Synvisc-One plus standardized physical therapy and sham injection plus standardized physical therapy at the stated follow-up timepoints.
That absence is not evidence that the groups had equal scores, nor is it evidence that one group had better scores. Without group means or an estimated between-group difference, the outcome cannot be quantified. Without a confidence interval or another uncertainty measure, its precision cannot be judged. Without a defined threshold for clinical importance in the registry record, even a numerical difference would need additional context to assess its practical meaning.
The trial's hypothesis about physical therapy compliance, performance, knee function, and pain is an intended rationale. The record does not report results for compliance or performance, and the primary outcome listed is the KOOS pain subscale. The proposed pathway from treatment to physical therapy participation and then to pain or function should not be mistaken for a demonstrated mechanism.
The registry lists the study as terminated, but does not report the reason. That status does not explain whether follow-up was complete, whether the primary analysis was performed, or why results are absent from the record. The enrollment entry does not indicate how many participants contributed outcome data at each timepoint.
The adverse-event entries offer limited descriptive counts, but they cannot answer the efficacy question and do not, by themselves, establish comparative safety. The study design label and treatment descriptions likewise do not establish a treatment effect. The defensible interpretation is limited: the registry describes a randomized comparison and its intended pain endpoint, while the primary outcome estimate and its uncertainty are not reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically informative as an example of the distinction between a stated research question and an analyzable result. The registry identifies a randomized comparison, the outcome scale, its direction, and assessment timepoints. Those details explain what the study aimed to compare. Without reported group scores or an estimated contrast, however, they do not tell readers what the comparison found.
The trial also illustrates why a study's status and enrollment entry cannot substitute for outcome reporting. Termination does not reveal the direction of an effect, and enrollment alone does not show how many observations informed each timepoint. Clear reporting of participant flow, analysis populations, missing data, and estimates with uncertainty would be needed to evaluate the primary result.
The two timepoints make the analysis plan important. In general, a prespecified approach can clarify whether results at both timepoints are confirmatory, how their dependence is handled, and whether multiplicity is addressed. The registry record does not give this information. The gap is especially relevant when readers might otherwise treat multiple timepoint comparisons as interchangeable evidence.
Finally, the registry's description of a double-masked study alongside an unblinded treating physician underscores the value of identifying who was masked and how. Masking is not a label that alone establishes protection against bias. These design and reporting details matter because they help readers judge the credibility and precision of an estimate, not because they determine its direction in advance. Here, the key primary estimate is not reported, so the statistical lesson is chiefly about what cannot be concluded from design descriptions and limited registry entries.
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 main trial-specific limitation in interpreting the registry record is the absence of numerical primary outcome results. There are no group means, standard deviations, estimated differences, confidence intervals, or p-values. As a result, the central pain-score comparison cannot be evaluated for magnitude, direction, or precision.
The primary outcome spans 12 and 24 weeks, but the record does not explain whether both timepoints were analyzed separately or jointly, whether either was designated as more important, or how multiplicity was handled. It also does not report outcome counts at each timepoint, missing-data methods, analysis populations, or baseline-adjustment methods. The reported enrollment of 42 cannot fill these gaps.
The study is listed as terminated, but the reason is not reported in the registry record. It is also not clear from the record whether the planned assessments were completed. The record labels the study double masked but does not specify who was masked; it describes an unblinded treating physician in the Synvisc-One arm. Details about random sequence generation and allocation concealment are not reported.
The intervention descriptions are incomplete, and the record does not provide results for the physical therapy compliance and performance concepts in the study hypothesis. It gives limited adverse-event counts without the contextual details needed to assess exposure time, event collection, or attribution. These reporting gaps constrain interpretation; they do not establish what the unreported findings would have been.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Optimization of Synvisc-One for Knee OA — NCT02029703.
- Registry record last updated 2017-04-21; status last verified 2017-03.
- Results first posted 2017-04-21.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
The registry record describes a randomized, double-masked, parallel-group trial of Synvisc-One injection plus standardized physical therapy versus sham injection plus standardized physical therapy for primary knee osteoarthritis. Enrollment is listed as 42, and study status is terminated. The primary outcome is the between-group difference in mean KOOS pain subscale score at 12 and 24 weeks; the scale ranges from 0 to 100, with higher scores indicating better status.
No primary outcome analyses or numerical results are listed. The reason for termination, statistical analysis plan, analysis populations, and missing-data methods are not reported in the registry record. Serious and other adverse-event counts are recorded by group, but the registry entries do not provide enough context for a full comparative safety assessment. The available record supports description of the intended comparison, not an estimate of its primary outcome effect.