ORTHOVISC Shoulder Osteoarthritis Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for ORTHOVISC Shoulder Osteoarthritis Study (NCT00436969), a randomized phase 3 study. The primary outcome is Visual Analog Scale (VAS) Pain Score (Per Protocol).

2. Clinical Question

The study addresses a comparison between two injection regimens for pain due to shoulder osteoarthritis. Its primary endpoint is a continuous pain score, not a responder outcome: it compares the group-level VAS score at 6 months in the defined per-protocol population. The registry record also lists responder measures and other pain and shoulder-function outcomes at different follow-up times and in different analysis populations. Those outcomes are secondary to the stated primary question.

The result should be read as an estimate of the difference between the groups in this trial, together with its uncertainty. It does not by itself establish what caused any observed difference, or determine whether a difference would be important to individual participants. The registry record does not report a threshold for a clinically important difference or the original design assumptions used to plan the trial.

3. Trial Design

This was a randomized, double-masked, parallel-group, phase 3 trial sponsored by DePuy Mitek. The registry record lists an enrollment of 274 and a completed status. The study began in 2006-12, and primary completion was recorded in 2010-02. Its stated purpose was to compare Orthovisc with corticosteroid injections in the shoulder for pain due to osteoarthritis.

The investigational arm received a one-time 8 mL dose of Orthovisc. The control arm received prescribed anesthetic and corticosteroid in an equivalent volume of 8 mL. The record describes the participants as randomized and the study as double masked; further details of how randomization was generated or implemented, and how masking was maintained, are not reported in the registry record.

The primary endpoint was the per-protocol VAS pain score at 6 months. The primary analysis population was defined as participants who received treatment and completed 6 months of follow-up without a major protocol deviation. The reported arm sizes for this endpoint were 58 in the control group and 107 in the investigational group. These endpoint analysis counts are not the same as the total enrollment; reasons for the difference are not reported in the registry record.

The registry record lists 22 outcome measures and 22 analyses, including secondary VAS and American Shoulder and Elbow Surgeons Evaluation Form outcomes. It identifies results for per-protocol and as-treated populations among the secondary measures. The original sample-size justification, detailed statistical analysis plan, and any interim-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.

Before assignment: Four subjects were randomized; however due to required imaging inclusion/exclusion criteria was not met. Hence, these 4 subjects were not treated.

Overall Study

Analysis population for the primary outcome, as defined in the registry: The Per Protocol analysis population was defined as all subjects that received treatment and completed 6 months of follow-up without a major protocol deviation.

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.

Population: The number of partipants analyzed were all 270 subjects that received treatment (87 control, 183 investigational).

6. Primary Endpoint

The registry lists the primary outcome as Visual Analog Scale (VAS) Pain Score (Per Protocol), measured over 6 Months.

The primary endpoint is the Visual Analog Scale pain score at 6 months in the per-protocol population. Participants’ scores are measured on a 100 mm scale: lower scores indicate less pain, and higher scores indicate greater pain. A continuous score retains information across the scale rather than reducing each participant to a responder or non-responder category. The registry record also includes responder outcomes as secondary measures.

The reported primary arm estimates are least-squares means, with standard errors as the dispersion measure. The analysis compares the adjusted group means, rather than simply comparing raw participant-level values. The registry reports an adjusted mean difference from a Mixed Models Repeated Measures ANCOVA. The endpoint is used to summarize pain at a specified follow-up time and to estimate the average difference between the randomized groups within the defined analysis population.

A group mean is not a description of every participant’s experience. It does not show the full distribution of scores or how many individuals improved by a particular amount. The registry record does not report a threshold for a clinically important VAS change, so the size of the estimated mean difference cannot be translated into that clinical interpretation from these results alone.

7. Results Posted in the Registry

• Investigational: mean 28.92 versus 30.39 on control; difference -1.47 (95% CI -8.86 to 5.91), standardized effect d = -0.06; z-test p = 0.696.

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.

Percentage of Responders Using the Visual Analog Scale (VAS) Pain Score (Per Protocol)

• 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:
  • Investigational: 63.6% (68/107) versus 63.8% (37/58) on control; risk difference -0.2 percentage points (95% CI -15.6 to 15.1), risk ratio 1.00 (0.78–1.27); unadjusted two-proportion z-test p = 0.975.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Investigational and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Responders Using the Visual Analog Scale (VAS) Pain Score (As Treated)

• 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:
  • Investigational: 54.4% (74/136) versus 59.7% (40/67) on control; risk difference -5.3 percentage points (95% CI -19.7 to 9.1), risk ratio 0.91 (0.71–1.17); unadjusted two-proportion z-test p = 0.475.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Investigational and the control. The interval gives the range of effects that remain compatible with the data.

Visual Analog Scale (VAS) Pain Score Change From Baseline and 12 Weeks (Per Protocol)

• 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:
  • Investigational: mean -24.49 versus -23.62 on control; difference -0.87 (95% CI -8.67 to 6.93), standardized effect d = -0.04; z-test p = 0.827.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Investigational and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists a broad set of secondary pain and shoulder-function measures, including responder outcomes, VAS change scores, and American Shoulder and Elbow Surgeons Evaluation Form patient scores. Results are identified for per-protocol and as-treated populations and for different follow-up times. The available numerical secondary results include responder analyses and a VAS change analysis; numerical results for other listed secondary outcomes are not reported in the registry record.

The available secondary findings do not materially change how the primary result should be read: they are additional, distinct outcomes rather than a replacement for the prespecified primary endpoint. The responder measure turns pain scores into a categorical outcome, while a change score addresses movement from baseline. These measures answer related but not identical questions, and their analysis populations differ from the primary per-protocol population.

Secondary outcomes usually carry less weight when many outcomes are assessed without a clearly reported multiplicity strategy. Testing several outcomes can increase the chance that at least one result appears noteworthy by chance. The registry record does not report an adjustment for multiple comparisons or a hierarchy specifying which secondary outcomes should control interpretation. The secondary p-values are unadjusted, so they should be viewed as exploratory evidence rather than as independent confirmation of the primary result.

Differences in denominators and analysis populations also matter. Per-protocol and as-treated analyses include different sets of participants, so apparent differences between their results can reflect both the endpoint and who was analyzed. The registry record does not report enough detail to attribute any such difference to a particular cause. Taken together, the secondary outcomes provide context, but they do not remove the uncertainty in the primary comparison.

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

• Percentage of Responders Using the Visual Analog Scale (VAS) Pain Score (Per Protocol)
• Percentage of Responders Using the Visual Analog Scale (VAS) Pain Score (As Treated)
• Visual Analog Scale (VAS) Pain Score Change From Baseline and 12 Weeks (Per Protocol)
• Visual Analog Scale (VAS) Pain Score Change From Baseline and 12 Weeks (As Treated)
• American Shoulder and Elbow Surgeons Evaluation Form (ASES) Patient Score Change From Baseline and 12 Weeks (Per Protocol)
• American Shoulder and Elbow Surgeons Evaluation Form (ASES) Patient Score Change From Baseline and 12 Weeks (As Treated)
• American Shoulder and Elbow Surgeons Evaluation Form (ASES) Patient Score Change From Baseline and 6 Months (Per Protocol)
• American Shoulder and Elbow Surgeons Evaluation Form (ASES) Patient Score Change From Baseline and 6 Months (As Treated)

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: it is a VAS pain score measured in millimeters. For a continuous outcome, a mean difference describes the contrast between the groups’ average scores. Here, negative differences correspond to a lower estimated score in the investigational group than in the control group, given the reported comparison order. Since the scale defines lower scores as less pain, the direction is interpretable, but the point estimate still needs to be considered alongside its uncertainty.

The sponsor reports least-squares means and an adjusted mean difference from Mixed Models Repeated Measures ANCOVA. In general, ANCOVA estimates a group contrast while accounting for covariates included in the analysis. Repeated-measures methods are designed to analyze outcome measurements collected over time and account for their relationship within participants. The specific covariates, model specification, handling of missing observations, and other implementation details are not reported in the registry record. The method name alone does not establish which adjustments were made.

The registry gives standard errors for the arm-level least-squares means. A standard error describes the estimated sampling uncertainty of an estimate; it is not the spread of individual participants’ pain scores. The sponsor’s adjusted confidence interval is reported directly. The separate recalculation is an approximate, unadjusted comparison made from posted summary statistics. Because that recalculation does not reproduce the sponsor’s repeated-measures adjusted analysis, its interval and test should be treated as a secondary statistical reading, not as the trial’s primary analysis.

A confidence interval describes a range of estimates compatible with the data and the stated analysis under its assumptions. It is not a range containing a specified proportion of individual participants’ outcomes. When an interval spans the null value, the data do not rule out no group difference at the corresponding confidence level. That does not prove there is no difference, and it does not demonstrate equivalence. Equivalence or non-inferiority requires a prespecified margin and a design and analysis suited to that question; such a margin is not reported in the registry record.

The reported p-value is 0.696 for the sponsor’s primary comparison. In general, a p-value describes how incompatible the observed data are with a specified null model, assuming the analysis conditions hold. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The registry record labels the analysis as superiority or other; a detailed hypothesis-testing plan and any prespecified decision threshold beyond the information in the record are not reported.

The recalculated p-value is also 0.696, but it comes from a simple unadjusted calculation. Its estimate is -1.472 and its confidence interval is -8.857 to 5.913, compared with the sponsor’s adjusted interval of -8.888 to 5.943. The slight interval difference is consistent with the calculations not being identical in method. The recalculation uses an approximate standard deviation derived from the reported standard errors; it does not recreate participant-level data or the sponsor’s model.

For the binary secondary responder outcome, a risk difference contrasts the observed proportions classified as responders. In general, a risk difference of no difference corresponds to the null value. The responder results also include confidence intervals and unadjusted p-values. Binary outcomes discard some information contained in the original continuous score by categorizing participants, and the meaning of “responder” depends on its definition. The registry record does not give further details of the responder threshold in the outcome description.

Over-dispersion is a general concern when a model for count or binary data assumes less variability than the data contain; if not addressed, uncertainty can be understated. It is not a reported feature of this continuous primary endpoint, and the registry record does not describe an over-dispersion adjustment. More generally, interpretation of any model-based estimate depends on its assumptions and implementation, which cannot be fully assessed from the reported method name and summary results alone.

11. Confidence Intervals and Precision

The primary sponsor-reported 95% confidence interval for the adjusted mean difference is -8.888 to 5.943. Its span across the null value means the data are compatible with group differences in either direction, as well as with no difference. The estimated difference of -1.472 is therefore not a precise determination of the direction or size of a group contrast.

A confidence interval conveys uncertainty about an estimated group-level quantity under the analysis and its assumptions. It is not a prediction interval for individual pain scores, and it does not mean that a fixed percentage of participants had outcomes inside its limits. The registry record reports the least-squares means with standard errors and reports the adjusted comparison with a 95% interval; it does not report a clinically important difference threshold. Statistical precision and clinical importance are distinct questions.

The recalculated unadjusted 95% confidence interval is -8.857 to 5.913. Its closeness to the sponsor interval is informative about the consistency of these summary-level calculations, but it does not make the analyses interchangeable. The sponsor result comes from Mixed Models Repeated Measures ANCOVA; the recalculation is approximate and unadjusted.

The interval’s width should be considered alongside the observed estimate, the analysis population, and the method. A non-significant result with an interval that includes both directions does not establish equivalence or rule out potentially meaningful differences. Whether any values within the interval would matter clinically cannot be determined from the registry record because the relevant threshold is not reported.

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 planning illustrations express required sample sizes as participants per arm for 80% power and participants per arm for 90% power. They are not total event counts: the event-count convention applies to time-to-event outcomes, whereas the primary outcome is continuous. The illustrations use the observed effect and show planning for 100%, 75%, and 50% of that effect.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. Under this illustration, the 80% power column describes the per-arm sample size that would give an 80% chance of detecting the target effect under the assumptions if that effect were the true one. The 90% column uses a higher chance of detection, and therefore requires a larger planned sample size for the same target effect.

Smaller target effects require more participants: planning for 75% or 50% of the observed effect entails larger per-arm estimates than planning for the full observed effect. The estimates are particularly large for some comparisons because the observed contrasts are small. They should not be interpreted as proof that the study was underpowered, nor as a reconstruction of the original enrollment plan. The original design assumptions and sample-size justification are not reported in the registry record. These figures are planning illustrations, not observed power.

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 = -1.472; pooled standard deviation σ = 23.104.
2. n = 2 × (1.96 + 0.842)² × 23.104² / -1.472² = 3,867.1, rounded up to 3,868 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 <- -1.472                      # observed difference in means
sigma <- 23.1037669475271                     # 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(436969)
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 = 3,868 (80% power), 5,177 (90% power)
 75% of observed effect: n per arm = 6,875 (80% power), 9,204 (90% power)
 50% of observed effect: n per arm = 15,469 (80% power), 20,708 (90% power)
power.t.test: 3868.1 
Simulated power at n = 3,868 per arm: 0.802 (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 primary analysis as a Mixed Models Repeated Measures ANCOVA, with an adjusted mean difference of -1.472, a 95% confidence interval from -8.888 to 5.943, and p = 0.696. That is the analysis reported for the trial’s primary endpoint and should be distinguished from the separate recalculation.

The recalculation uses posted summary statistics to make an approximate, simple unadjusted comparison. It estimates the same mean difference, -1.472, with a 95% confidence interval from -8.857 to 5.913 and an unadjusted p-value of 0.696. The small differences in the interval limits reflect that the recalculation is not the sponsor’s model-based analysis. It does not use the participant-level data or reproduce the repeated-measures ANCOVA.

The registry does not flag a discrepancy between the posted sponsor result and the recalculation. Even so, the recalculated result should be read as a supplementary check, not as a replacement for the trial’s own reported analysis. Both intervals include the null value, and both p-values are 0.696; neither result establishes a difference between the groups or establishes equivalence.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists 22 outcome measures and 22 analyses, including several pain and shoulder-function measures, time points, and analysis populations. Assessing many outcomes raises a multiplicity issue: when multiple statistical tests are conducted, the chance of a seemingly unusual result somewhere among them can increase. In general, a prespecified testing hierarchy or multiplicity adjustment can help define how results should be interpreted. Neither an adjustment strategy nor a hierarchy is reported in the registry record.

The primary endpoint is identified as the per-protocol VAS pain score at 6 months, and its sponsor-reported analysis is identifiable. The record also identifies secondary outcomes, but the original protocol and full statistical analysis plan are not reported. It is therefore not possible to determine from the registry entry whether all analysis decisions, outcome definitions, or testing priorities were set before results were examined.

The registry defines the per-protocol population as participants who received treatment and completed 6 months of follow-up without a major protocol deviation. It also reports as-treated secondary analyses. These populations answer different analysis questions, and the numerical denominators differ. The record does not report the number or reasons for participants excluded from the primary endpoint analysis, the extent or pattern of missing outcome data, or the specific methods used to handle missing observations in the sponsor’s repeated-measures analysis. These details are important for judging the potential influence of missing data.

Randomization supports a comparison between assigned groups, while analysis choices and departures from follow-up can affect how closely a particular analysis preserves that comparison. The registry record does not report enough information to assess those issues fully. No interim-analysis plan, stopping rule, or detailed original design assumptions are reported in the registry record. These omissions limit assessment of how the final analysis was planned and how all reported outcomes should be weighed together.

16. 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: breast cancer (1.1%), quadruple bypass 5/6/09 (1.1%), iliopsoas abscess (1.1%), shoulder pain (index shoulder) right shoulder (1.1%), total shoulder arthroplasty plus bone graft glenoid scapular right shoulder (1.1%).

The adverse-event record lists 87 control participants and 183 investigational participants as at risk for serious adverse events. Serious adverse events affected 3 participants in the control group and 10 in the investigational group. For other adverse events, the at-risk counts are 87 and 183, and the affected counts are 6 and 19, respectively. These are counts, not percentages, and the registry record does not provide exposure-adjusted rates or further context for interpreting the difference in group sizes.

The listed serious-event terms include Breast Cancer, Quadruple Bypass 5/6/09, Iliopsoas Abscess, Shoulder Pain (Index Shoulder) Right Shoulder, and Total Shoulder Arthroplasty Plus Bone Graft Glenoid Scapular Right Shoulder, each recorded as 1.1%; Chest Pain - Cardiac Cath to Rule Out Cad is recorded as 0.5%. These entries describe events reported in the registry; they do not establish that an injection caused an event. Death counts are not reported in the registry record.

Adverse-event counts should be considered as part of the trial record, not as a complete assessment of safety. The registry entry does not provide additional information about event timing, severity categories beyond serious versus other, or causal assessments.

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

The primary result estimates the difference in average 6-month VAS pain scores between the two randomized groups in the per-protocol population. The sponsor-reported adjusted mean difference is -1.472, with a 95% confidence interval from -8.888 to 5.943 and p = 0.696. The estimate is numerically in the direction of a lower score in the investigational group, but the interval includes the null value and extends in both directions.

This result does not establish a difference between the groups. It also does not establish that the groups are equivalent or that meaningful differences have been ruled out. The interval shows uncertainty in the estimate, and the registry record does not state a clinical-importance threshold against which its values can be judged. A group average does not describe every participant, and the mean comparison does not indicate how many people experienced a particular level of change.

The finding applies to the endpoint and population analyzed: the per-protocol VAS score at 6 months. It should not be automatically generalized to every person with shoulder osteoarthritis, other follow-up times, other outcomes, or the as-treated population. The enrolled number and the endpoint analysis counts differ, and reasons for that difference are not reported in the registry record.

The secondary outcomes offer related measurements but involve different definitions, time points, and analysis populations. Because a multiplicity plan is not reported, unadjusted secondary findings carry additional uncertainty. The record also does not report the original sample-size justification or enough detail about missing-data handling to resolve all questions about the design and analysis.

These are statistical limits on what can be concluded from the posted results, not medical advice. The trial’s estimates describe the observed comparison and its precision; they do not by themselves prove benefit, harm, or lack of effect.

18. Why This Trial Matters Statistically

This trial illustrates why an estimated difference and its uncertainty should be interpreted together. The primary point estimate is -1.472, but the sponsor-reported 95% confidence interval ranges from -8.888 to 5.943. Focusing only on the point estimate would conceal the range of group differences compatible with the analysis. Focusing only on the p-value would also miss the direction and uncertainty of the estimate.

It also shows why analysis populations need clear definitions. The primary endpoint uses a per-protocol population defined by treatment receipt, completion of 6 months of follow-up, and absence of a major protocol deviation. The registry separately lists as-treated analyses, with different endpoint counts. Those results are not direct substitutes for one another, and the reasons for the varying denominators are not reported.

The contrast between sponsor and recalculated results is useful methodologically. A simple summary-statistic calculation can provide a check, but it does not reproduce an adjusted repeated-measures analysis. Similar estimates do not make the methods identical, and model-based results depend on specifications that are not fully described in the registry record.

Finally, the record includes multiple outcomes and populations without reporting a multiplicity strategy. That makes it important to distinguish the primary endpoint from secondary analyses and to avoid treating unadjusted secondary findings as independent confirmation. These features make the study a practical example of how design, population, precision, and reporting detail all shape statistical interpretation.

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 report the detailed protocol or statistical analysis plan, including the randomization procedure, covariates in the primary model, or detailed handling of missing data. Although the primary method is named as Mixed Models Repeated Measures ANCOVA, the method label alone is not sufficient to reproduce or fully assess the analysis.

The primary endpoint is analyzed in a per-protocol population, while the overall enrollment is 274 and endpoint counts are 58 and 107. Reasons for the difference are not reported in the registry record. Per-protocol eligibility depends on follow-up completion and protocol-deviation criteria, so the analyzed participants may not represent all randomized participants in the same way as an analysis based on assignment. The registry does not provide enough detail to evaluate the impact of exclusions or missing outcomes.

The primary confidence interval spans the null value, and no clinical-importance threshold is reported. Thus, the clinical meaning of the range cannot be determined from the record alone. The original sample-size justification is also not reported; planning illustrations based on observed effects should not be mistaken for the trial’s original design rationale.

The record lists many outcomes and analyses but does not report a multiplicity adjustment or testing hierarchy. Numerical results are not reported for all listed outcomes in the available record. The adverse-event counts also have different at-risk denominators between groups, and the registry does not provide further context, exposure-adjusted rates, or death counts. These reporting limitations restrict how comprehensively efficacy and safety can be assessed from this record.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: ORTHOVISC Shoulder Osteoarthritis Study — NCT00436969.
• Registry record last updated 2017-03-09; status last verified 2016-11.
• Results first posted 2014-04-11.
• 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

The ORTHOVISC Shoulder Osteoarthritis Study was a randomized, double-masked, parallel-group, phase 3 trial sponsored by DePuy Mitek. The registry records 274 enrolled participants, a completed status, a start date of 2006-12, and primary completion in 2010-02.

The primary endpoint was the per-protocol VAS pain score at 6 months. The sponsor reported an adjusted mean difference of -1.472, with a 95% confidence interval from -8.888 to 5.943 and p = 0.696. The interval includes the null value, and the registry record does not report a clinical-importance threshold.

The record lists multiple secondary outcomes, analysis populations, and adverse-event counts. Multiplicity procedures, original design assumptions, and important details about missing data are not reported in the registry record, limiting assessment beyond the posted analyses.