Cingal Study for Knee Osteoarthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cingal Study for Knee Osteoarthritis (NCT01891396), a randomized na study. The primary outcome is Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (ITT).

2. Clinical Question

3. Trial Design

The registry describes a randomized, double-blind, parallel-group, multicenter study of a single injection for knee osteoarthritis. The listed interventions were Cingal®, Monovisc®, and saline. The Cingal® injection combined sodium hyaluronate with triamcinolone hexacetonide; Monovisc® contained sodium hyaluronate; saline was the comparison injection. Each was described as a single 4 milliliter unit dose.

The registry records an enrollment of 368 and a completed study. The study start is recorded as 2013-06 and primary completion as 2014-05. The phase is listed as NA. Further explanation of the phase designation is not reported in the registry record.

Random allocation means that treatment assignment was not described as being chosen solely by participants or investigators. Double masking indicates that the study was recorded as double-blind, but the registry record does not describe which parties were masked or the procedures used to maintain masking. The parallel-group model means that participants were assigned to a study group rather than crossing through multiple treatments, as described by the registry design label.

The primary endpoint is the change in WOMAC Pain Score from baseline to 12 weeks, comparing Cingal® with saline in the Intent To Treat population. The registry also lists secondary assessments involving WOMAC pain, responder status, and global assessments, with comparisons involving saline or Monovisc®. The full protocol, the original sample-size justification, and the trial’s detailed statistical analysis plan are not reported in the registry record. The study’s recorded purpose was to assess symptomatic relief and safety after a single knee injection.

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: The most common reason that subjects were excluded before being assigned to a study group (screen failures) was that enrollment target had been reached while subjects were in screening process. Other reasons for screen failure included radiological failures; Kellgren-Lawrence grade not meeting eligibility in the index or contralateral knee.

Overall Study

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 Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (ITT), measured over 12 Weeks.

The primary endpoint is change in knee pain from baseline to 12 weeks, measured by the WOMAC Pain Score in the Intent To Treat population. The score is described as a validated visual analog scale extending from 0 mm, meaning no pain, to 100 mm, meaning the highest pain level. The endpoint is a continuous measure: the analysis summarizes the average change in each group rather than classifying each participant only as a responder or non-responder.

The direction of change matters. A negative change indicates reduced pain from baseline, and a more negative change indicates a greater reduction. This convention helps interpret the comparison: the group with the more negative mean change has a larger average decrease on this measure. It does not, by itself, describe every participant’s experience or establish how meaningful a particular difference is to patients.

A baseline-to-follow-up change score is used to express how the measured outcome moved over the study period. The 12-week timeframe identifies when the primary comparison was assessed; it should not be read as evidence about effects outside that assessment period. The registry names the score and its scale but does not report a threshold for a clinically important difference. Therefore, statistical evidence about a group contrast and the clinical importance of that contrast are separate questions.

7. Results Posted in the Registry

• Hyaluronic Acid (Monovisc®): mean -36.10 versus -40.20 on control; difference 4.10 (95% CI -0.48 to 8.68), standardized effect d = 0.20; z-test p = 0.079.
• Saline: mean -31.00 versus -40.20 on control; difference 9.20 (95% CI 3.59 to 14.81), standardized effect d = 0.45; z-test p = 0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (ITT)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Hyaluronic Acid (Monovisc®): mean -29.60 versus -34.60 on control; difference 5.00 (95% CI 0.22 to 9.78), standardized effect d = 0.24; z-test p = 0.040.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Hyaluronic Acid (Monovisc®) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

OMERACT-OARSI Responder Index Comparing Cingal® to Saline (ITT)

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Saline: 82.6% (57/69) versus 91.9% (137/149) on control; risk difference -9.3 percentage points (95% CI -19.3 to 0.6), risk ratio 0.90 (0.80–1.01); unadjusted two-proportion z-test p = 0.040.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Saline and the control. The interval gives the range of effects that remain compatible with the data.

Patient Global Assessment (PGA) Comparing Cingal® to Saline (ITT)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Saline: mean -25.30 versus -36.50 on control; difference 11.20 (95% CI 5.55 to 16.85), standardized effect d = 0.57; z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Saline than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary assessments involving WOMAC pain, responder status, and patient or evaluator global assessments. The detailed posted secondary results cover more than one measurement type and more than one comparison. Their overall pattern is broadly compatible with the direction of the primary pain result in some comparisons, but the strength and precision of evidence vary. These outcomes provide supporting context, not a single unified test of the primary question.

Secondary endpoints can help show whether an observed pattern extends beyond one instrument or assessment time. At the same time, a responder index and a continuous pain score do not measure exactly the same thing. Global assessments also reflect different evaluations from the WOMAC pain scale. Agreement across measures may be informative, but differences between them are not necessarily contradictions because their definitions, scales, and comparisons differ.

Unadjusted secondary results carry less weight when many outcomes and comparisons are examined. Each additional test creates another opportunity for a chance finding, and the registry record does not report a multiplicity adjustment strategy. A nominally small p-value for one secondary measure therefore should not be treated as if it were the sole prespecified primary test. This consideration does not mean that secondary outcomes are uninformative; it means their evidential role depends on how they were planned and analyzed.

The record lists 24 posted secondary outcomes, but a full account of the prespecified hierarchy, handling of repeated measures, missing data, and multiplicity control is not reported in the registry record. Without those details, the secondary results are best interpreted as exploratory or supportive evidence rather than as independent definitive proof. They do not replace the primary comparison or resolve the discrepancy between the sponsor’s analysis and the summary-statistic recalculation.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (ITT)
• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Monovisc® (ITT)
• OMERACT-OARSI Responder Index Comparing Cingal® to Saline (ITT)
• Patient Global Assessment (PGA) Comparing Cingal® to Saline (ITT)
• Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (ITT)
• Patient Global Assessment (PGA) Comparing Cingal® to Monovisc® (ITT)
• Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain Score Comparing Cingal® to Saline (ITT)
• Evaluator Global Assessment Comparing Cingal® to Saline (ITT)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous, and the registry reports group means and standard errors for WOMAC Pain Score change. A mean describes the average change in a group. A standard error describes the uncertainty in the estimated group mean; it is not the spread of individual participants’ scores. The standard errors help quantify how precisely the means are estimated, while the group counts also inform the precision of a comparison.

What does the mean difference represent?

The recalculated contrast is expressed as the mean change in the comparison group minus the mean change in Cingal®. Because a more negative change indicates greater pain reduction, a positive contrast corresponds to a more negative average change in the Cingal® group. This direction can initially seem counterintuitive: the positive contrast does not mean that the Cingal® group had a positive change in pain. The arm means and the endpoint’s sign convention are needed to interpret it correctly.

The recalculated continuous comparisons use posted summary statistics to estimate an unadjusted difference in means and its confidence interval. This is a simple re-analysis of the reported summaries, not a reconstruction of the sponsor’s full model or individual-participant analysis. It does not account for any adjustments or analysis choices that may have been used by the study investigators unless those choices are explicitly reflected in the posted result. The registry record does not report the full statistical analysis plan.

What does a confidence interval convey?

A confidence interval gives a range of estimates compatible with the observed data under the method used. A narrower interval indicates greater precision than a wider interval. For a difference, an interval containing zero includes the possibility of no group difference under that analysis; an interval excluding zero indicates that zero is not among the values covered by that interval. Neither feature alone determines whether the difference matters clinically. The interval also depends on the assumptions and the summary data used to calculate it.

The p-value addresses how unusual the observed result, or a more extreme result, would be under a null model of no difference and the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the magnitude or clinical importance of a difference. The recalculated p-values are unadjusted. They should be read alongside the estimated difference and its interval, not in isolation.

Why distinguish the sponsor analysis from a recalculation?

The registry reports a sponsor analysis using ANOVA for the primary Cingal®-versus-saline comparison. It also reports a separate recalculation based on the posted group summaries. Those results are not identical. An analysis using participant-level information or a specified model can differ from a calculation based only on summary measures. The record does not provide enough detail to reconcile the differences. For that reason, the sponsor’s own analysis takes precedence; the recalculation is a transparent, unadjusted check rather than a replacement for the sponsor’s analysis.

For a binary outcome, such as responder status, the comparison can be expressed as a risk difference: the group proportions are subtracted. A risk difference near zero indicates similar observed proportions, while a difference farther from zero indicates a larger observed separation. Its confidence interval describes uncertainty in that separation. Risk ratios and odds ratios are alternative ways to express binary contrasts, but they answer the question on different scales. They should not be conflated with the continuous mean difference used for WOMAC pain.

The registry’s reported secondary analyses include outcomes with different measurement types, including continuous scores and responder status. Statistical methods appropriate to one type of measure need not have the same interpretation as methods for another. A reported ANOVA p-value for a comparison does not provide the missing model details, such as covariate adjustment, assumptions, or how repeated observations were handled. Such details are not reported in the registry record.

Over-dispersion is a general issue for count outcomes: observed variation can exceed what a simple count model assumes, making uncertainty estimates too small if that extra variation is ignored. The primary endpoint is a continuous pain score, not a count outcome, so over-dispersion is not the central issue for interpreting its mean difference. More generally, the distribution and variability assumptions behind an analysis affect the validity of its standard errors and intervals. The registry record does not report diagnostic checks or detailed model assumptions, so those cannot be evaluated from the posted summaries.

11. Confidence Intervals and Precision

The primary recalculated Cingal®-versus-saline estimate is a mean difference of 9.2, with a confidence interval from 3.594 to 14.81. In the stated subtraction direction, positive values correspond to a more negative mean pain change in the Cingal® group. The interval stays above zero, so the recalculation is inconsistent with a zero difference at the confidence level used for the calculation. The registry record does not specify the confidence level for this recalculated interval, so a percentage level should not be inferred.

Precision is not the same as size or importance. The interval gives a range of estimates compatible with the analysis, rather than identifying the exact effect. It also does not show the distribution of participant-level outcomes. Even if an interval excludes zero, the record does not establish whether all values in the interval represent a clinically important difference. The registry does not report a threshold for clinical importance.

For Cingal® compared with Monovisc®, the recalculated mean difference is 4.1, with a confidence interval from -0.476 to 8.676. This interval includes zero and spans values on either side of it, reflecting uncertainty about whether the groups differed on this measure. It is less precise about the direction of a possible difference than an interval lying entirely on one side of zero.

The arm-level standard errors are estimates of the precision of the means, whereas the confidence intervals for the contrasts describe uncertainty in the between-group differences. These are related but distinct quantities. Interpretation should consider the estimated contrast, its interval, the endpoint direction, and the sponsor’s analysis. In this trial, the sponsor’s primary analysis differs from the simple recalculation, and that discrepancy is important when weighing precision claims.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations, not a report of the trial’s original design justification. For these continuous outcomes, the figures refer to participants per arm, not a combined total. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario uses a stated fraction of the observed effect as the effect to detect.

The 80% power column describes a planning target under which the calculation gives an 80% chance of detecting the specified effect if that effect is present and the assumptions hold. The 90% power column uses a higher chance of detection under the same general framing. These are design illustrations; they do not establish the probability that the trial’s result is correct or that a treatment effect exists.

Rows for 100% of the observed effect use the observed estimate as the planning target. Rows for 75% or 50% of the observed effect plan for a smaller effect. Smaller effects are harder to distinguish from random variation, so the calculations require more participants per arm to reach the stated power target. This is why the planning figures rise as the assumed effect becomes smaller.

The registry record does not report the trial’s original sample-size assumptions or justification. These illustrations use the observed effect and the stated planning assumptions, so they should not be read as the design method used for this trial. They are not observed power: observed power is not an additional interpretation of the result, and these calculations do not measure the chance that the observed finding is true. No time-to-event sample-size interpretation applies to the continuous primary outcome.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 4.100; pooled standard deviation σ = 20.180.
2. n = 2 × (1.96 + 0.842)² × 20.180² / 4.100² = 380.3, rounded up to 381 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 4.1                      # observed difference in means
sigma <- 20.1798546076658                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(1891396)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 381 (80% power), 510 (90% power)
 75% of observed effect: n per arm = 677 (80% power), 906 (90% power)
 50% of observed effect: n per arm = 1,522 (80% power), 2,037 (90% power)
power.t.test: 381.2 
Simulated power at n = 381 per arm: 0.804 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports the sponsor’s own primary comparison as an ANOVA superiority analysis with p = 0.010 for Cingal® versus saline. The simple recalculation from the posted group summaries gives an unadjusted p-value of 0.001 and a mean difference of 9.2, with a confidence interval from 3.594 to 14.81. These are not identical analyses or results.

The recalculation uses posted summary statistics and is unadjusted. The sponsor’s analysis may reflect its own analysis procedures, but the registry record does not provide enough detail to determine which analytic choices account for the difference. The sponsor’s own analysis takes precedence over the recalculation when describing the sponsor-reported result. The recalculation remains useful as a separate check of the displayed means and uncertainty, but it should not replace the analysis reported by the study sponsor.

Both results point to a group difference in the same general direction, given the more negative mean change in the Cingal® group and the endpoint’s sign convention. However, their p-values should not be combined or treated as independent confirmations. The discrepancy is a reason to retain the distinction between the sponsor’s inferential analysis and the unadjusted re-analysis, rather than selecting whichever result appears more favorable.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study tests several endpoints, time points, or treatment comparisons. Even if each individual test uses a conventional significance threshold, examining many tests increases the chance that some results will appear statistically notable by chance. The registry lists 26 outcome measures and 26 analyses, and it records 24 posted secondary outcomes. These figures indicate a broad set of reported analyses, but do not identify how many tests were planned, which were designated confirmatory, or whether an adjustment was used.

The primary endpoint is specifically identified as WOMAC pain change at 12 weeks comparing Cingal® with saline in the Intent To Treat population. That prespecified primary framing gives it a different interpretive role from secondary outcomes. However, the registry record does not report the trial’s detailed multiplicity strategy, any hierarchy among secondary outcomes, or whether p-values were adjusted for multiple comparisons. Unadjusted secondary p-values should therefore be treated cautiously.

The Intent To Treat population is named for the primary outcome, and the secondary outcome titles also identify ITT. The registry record does not give enough detail to assess how participants with missing measurements were handled, whether all randomized participants contributed to each analysis, or what imputation or sensitivity analyses were used. These are important because missing outcome data can affect both the estimated group contrast and its uncertainty. The endpoint-specific group counts are reported, but they do not explain the reasons for any difference between the group counts and overall enrollment.

The original trial sample-size justification, interim analyses, and full statistical analysis plan are not reported in the registry record. Those items should not be inferred from the post hoc planning illustrations or from the results. Without them, it is not possible to verify the planned power, the prespecified analysis sequence, or the handling of all possible multiplicity and missing-data decisions.

16. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: post-laminectomy syndrome (1.4%), mania disorder (1.4%), peripheral facial nerve damage (1.4%), benign neoplasm of adrenal gland (0.7%), herniated disc (0.7%).

The registry reports serious adverse events for 2 participants in the Cingal® group, 0 in the Monovisc® group, and 3 in the saline group. It reports no deaths in any of the three groups. These counts are presented with the corresponding at-risk group counts in the safety record, but the registry entry does not provide a detailed account of the events’ timing, duration, severity grading, or relationship to the study injection.

The record also lists other adverse events affecting 36 participants in the Cingal® group, 37 in the Monovisc® group, and 12 in the saline group. Serious and other adverse event counts are different reporting categories and should not be combined. The listed serious-event terms include post-laminectomy syndrome, mania disorder, peripheral facial nerve damage, benign neoplasm of adrenal gland, and herniated disc. The registry lists percentages beside those terms, but does not provide enough context in this entry to establish causality or compare event risk reliably.

These counts describe events recorded during the study; they do not establish that an injection caused an event, nor do they rule out uncommon or later harms. Exposure duration and detailed safety-analysis methods are not reported in the registry record. Safety interpretation should therefore remain descriptive and should not be inferred from the pain outcome analysis.

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

The primary outcome measures average change in a knee pain score over the period from baseline to 12 weeks. The posted group means show more negative change for Cingal® than for saline, and the sponsor reports an ANOVA superiority result for that comparison. The unadjusted recalculation also estimates a difference in the same direction, but its result is not identical to the sponsor’s. The sponsor’s analysis takes precedence as the study’s own reported analysis.

This is evidence about a group comparison in the enrolled trial, not a prediction for every person with knee osteoarthritis. An average difference does not show how many individuals improved, stayed the same, or worsened. Nor does a statistically discernible group difference establish that the size of the difference is important to patients. The registry record does not state a threshold for clinical importance.

The endpoint is tied to a specified scale and assessment time. It does not establish what happened at other times, how long any change might last, or whether other aspects of health changed. The study compared injections described in the registry; conclusions should not be extended to other interventions, dosing schedules, or populations not described in the record.

The secondary outcomes may add context, but the record does not report a full multiplicity plan, detailed missing-data methods, or the complete statistical analysis plan. This limits interpretation of secondary p-values and of the robustness of results to analytic decisions. Safety findings are also limited to the adverse event information posted in the registry and do not establish causation.

Overall, the posted data support a statistical comparison of mean pain change in this study, while leaving clinical importance, individual response, longer-term outcomes, and the full robustness of the analysis unresolved. Those are distinct questions from whether the observed group contrast differs from zero under a particular statistical analysis.

18. Why This Trial Matters Statistically

This trial illustrates why the direction and definition of an endpoint must be understood before reading a treatment contrast. The WOMAC measure is a change score where negative values mean pain reduction, so a more negative group mean represents a larger average reduction. A positive mean difference can therefore favor the group with the more negative change, depending on the subtraction direction. Reading the contrast without the endpoint convention could reverse its meaning.

It also demonstrates the distinction between a sponsor-reported analysis and a simple unadjusted recalculation from summary data. Both can be informative, but they are not interchangeable. When they differ, the sponsor’s own analysis takes precedence, and the discrepancy should remain visible rather than being resolved by choosing one result without explanation.

The trial also provides an example of how confidence intervals add information beyond p-values. They show the range of effect estimates compatible with an analysis and help convey precision, while not answering whether the difference is clinically important. Secondary outcomes introduce another statistical challenge: numerous measures and comparisons make isolated unadjusted findings less persuasive than a prespecified primary comparison.

Finally, the record distinguishes an observed trial result from hypothetical planning calculations. Sample-size illustrations based on an observed effect can show how smaller target effects require more participants under stated assumptions, but they do not reconstruct the original design or indicate observed power. These distinctions are central to responsible reading of clinical trial results.

19. 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 registry record does not include the full protocol or statistical analysis plan. As a result, the intended hierarchy of outcomes, detailed model specifications, prespecified covariate adjustments, and multiplicity procedures cannot be assessed. Although the primary endpoint is identified, this missing information limits evaluation of whether all reported comparisons followed the original analysis plan.

The record names the Intent To Treat population but does not explain how missing primary or secondary measurements were handled. It also does not give reasons for differences between the overall enrollment and the endpoint-specific group counts. Without missing-data methods and sensitivity analyses, the potential influence of incomplete outcome data cannot be evaluated.

The recalculated confidence intervals and p-values are based on posted summary statistics and are not the sponsor’s complete analysis. The sponsor’s own analysis takes precedence where the results differ. The available information does not allow the difference between these analyses to be resolved. The registry also does not report a clinically important difference threshold for the WOMAC scale, limiting interpretation of the practical importance of the estimated contrast.

The record covers a specific single-injection design and reports the primary outcome at 12 weeks. It does not establish the duration of any effect outside that timeframe. Safety reporting is limited to the posted adverse event counts and selected terms; details about timing, attribution, exposure, and event management are not reported. These constraints mean the results should be interpreted as registry-record evidence about the described trial rather than a complete account of its methods or all possible outcomes.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Cingal Study for Knee Osteoarthritis — NCT01891396.
• Registry record last updated 2023-06-01; status last verified 2023-05.
• Results first posted 2022-05-12.
• 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.

23. Record Summary

NCT01891396 is a completed randomized, double-blind, parallel-group, multicenter study of a single injection for knee osteoarthritis. The listed groups received Cingal®, Monovisc®, or saline. Enrollment is recorded as 368, with the study start in 2013-06 and primary completion in 2014-05.

The primary endpoint was change in WOMAC Pain Score from baseline to 12 weeks in the Intent To Treat population. More negative change represents greater pain reduction. The sponsor reports an ANOVA superiority analysis for Cingal® versus saline; a simple recalculation from the posted summaries differs and should not replace the sponsor analysis.

The record also lists secondary pain, responder, and global assessment outcomes, as well as adverse event counts. The detailed statistical analysis plan, original sample-size justification, multiplicity strategy, and missing-data methods are not reported in the registry record.