A Study of Hyaluronan for the Treatment of Osteoarthritis in the Thumb: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Hyaluronan for the Treatment of Osteoarthritis in the Thumb (NCT00398866), a randomized phase 3 study. The primary outcome is Pain Visual Analogue Scale (VAS).

2. Clinical Question

The registry record describes a randomized comparison in thumb osteoarthritis. Its stated principal hypothesis was that hyaluronan would provide greater pain relief, higher patient satisfaction, and better functional outcomes than either local anesthetic or corticosteroid injection. It also states a hypothesis that corticosteroid would outperform local anesthetic on those outcomes. These are proposed questions, not evidence that one group had better results.

A further stated hypothesis concerned pretreatment function: patients with worse function before treatment were expected to have less improvement and worse post-treatment results after hyaluronan or corticosteroid. The record does not report results for that hypothesis. Satisfaction is named in the summary, but a corresponding outcome measure is not described in the record details. Function is represented by the Disabilities of the Arm, Shoulder and Hand (DASH) Questionnaire among the secondary outcomes.

The primary outcome is pain intensity on a 0-to-100 VAS, with 100 defined as severe pain. It is specified at baseline and 26 weeks, among patients who completed follow-up through 26 weeks. The registry record does not provide group means, standard deviations, changes, between-group contrasts, confidence intervals, or p-values. Consequently, the comparison that motivated the trial is clear, but the registry entries do not establish the magnitude or precision of any group difference.

3. Trial Design

This was a phase 3, randomized, triple-masked, parallel-group trial. The registry record gives enrollment as 200 and lists the status as completed. The sponsor is Hospital for Special Surgery, New York. The recorded study start is 2006-08, and the primary completion is 2013-03. The record does not specify which people or roles were masked, how the randomization sequence was generated, or how assignment was concealed.

The three listed arms were bupivacaine local anesthetic, triamcinolone corticosteroid, and Synvisc (Hylan G-F 20, hyaluronan). The corticosteroid arm description specifies triamcinolone (Kenalog) 40 mg. The brief summary characterizes local anesthetic injections as the placebo comparison. That wording does not make bupivacaine an inert substance; the registry identifies it as a local anesthetic injection. The record does not describe injection procedures, schedules, or other treatment details.

A parallel-group design assigns participants to a group and compares outcomes across groups rather than having each participant receive every intervention. This is a general description of the design, not a claim about the trial's allocation procedures beyond what is recorded. The registry identifies the allocation as randomized, but does not report whether allocation was equal or describe stratification or blocking.

The primary outcome is mean pain VAS at baseline and 26 weeks, with standard deviation as the dispersion measure and a stated population of patients completing follow-up through 26 weeks. DASH is listed as a secondary outcome. Although the record identifies two outcome measures, the details of the other measure and its timing are not fully described in the available record details. It reports zero analyses. The statistical analysis plan, analysis populations, sample-size justification, and handling of missing observations 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: 396 subjects screened 169 did not meet eligibility criteria 27 declined injection 200 subjects randomized

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients who completed follow-up through 26 weeks

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 Pain Visual Analogue Scale (VAS), measured over Baseline, 26 Weeks.

The primary endpoint is pain intensity measured with a Visual Analog Scale (VAS). The record describes scores ranging from 0 to 100 and defines 100 as severe pain. It specifies the outcome at baseline and 26 weeks, reports the measure as a mean, and identifies standard deviation as its dispersion measure. The stated primary-outcome population consists of patients who completed follow-up through 26 weeks.

A pain scale gives a numerical way to record a participant's reported symptom intensity. In general, continuous outcomes such as scale scores can be summarized by a group mean, while a standard deviation describes how spread out individual scores are around that mean. Neither statistic alone describes the uncertainty in a comparison between groups; that requires an estimate of the contrast and its uncertainty, such as a confidence interval.

Baseline and follow-up measurements can be used to describe pain at each time point or change over time, but those are not interchangeable analyses. A comparison might focus on follow-up scores, changes from baseline, or an adjusted model. Which approach was used in this trial is not reported in the registry record. The record also provides no group-level VAS means or standard deviations, and no estimated changes or treatment contrasts.

For that reason, the endpoint's scale and timing identify what the trial set out to measure but do not reveal the observed effect. Even the direction and precision of a group difference cannot be assessed from the endpoint description alone. The record's primary-outcome information is limited to the measure, summary type, dispersion type, timing, and follow-up population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean describe?

For a continuous outcome such as a VAS score, the mean is a measure of the group's average score. It condenses the observations into one summary, but does not show how individual scores are distributed. The standard deviation, which the registry identifies as the dispersion measure, describes spread around the mean. Two groups can have similar means but different spreads, or different means with substantial overlap among individual observations. The registry record does not report the actual means or standard deviations for this trial, so these concepts explain the proposed summary rather than characterize its observed results.

What would a between-group estimate add?

A comparison needs an estimate of the difference between groups, defined for a particular outcome and time point or change measure. In general, an estimate conveys the direction and size of the observed contrast, while a confidence interval conveys the range of values reasonably compatible with the data and the analysis assumptions. A confidence interval is not a guarantee that the true effect lies within its bounds. Its width is informative about precision: wider intervals indicate greater uncertainty than narrower ones. The registry record does not report a primary-outcome contrast or confidence interval.

A p-value, when used, addresses how compatible the observed data are with a specified null model under the assumptions of the test. It is not the probability that the null hypothesis is true, and it does not measure the clinical importance of an effect. The registry record does not report p-values for the primary outcome. Thus, neither statistical significance nor lack of statistical significance can be inferred.

Why does the chosen analysis matter?

Baseline and 26-week values permit several possible analytic approaches. A comparison could use the 26-week scores, changes from baseline, or a model that adjusts for baseline scores. These approaches target related but not identical quantities and may rely on different assumptions. A model could also account for repeated measurements if additional time points were collected, but the primary outcome description names baseline and 26 weeks. The registry record does not state which analytic approach was planned or used. It also does not describe covariate adjustment, model diagnostics, or the handling of departures from model assumptions.

Randomization is a design feature intended to support fair comparison of assigned groups, but it does not itself specify the analysis. In general, an analysis based on randomized assignment preserves the original group comparison, while analyses restricted to subsets can be affected by how participants enter those subsets. The primary-outcome population is described as people completing follow-up through 26 weeks, but the record does not say whether that was the only analysis population or how missing follow-up was addressed.

What does over-dispersion mean in general?

Over-dispersion is a general issue for count outcomes: observed variability can exceed what a simple model assumes. It can make standard errors too small if the extra variability is ignored. The primary endpoint in this record is a continuous pain score, not a count, and no count-outcome analysis is reported. Over-dispersion therefore should not be invoked as an explanation for any result from this trial; it is a general statistical concept rather than a reported trial method.

What do the sample-size assumptions describe?

The registry includes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect. These are described as planning illustrations computed from the observed effect, not as the trial's own design. Any resulting sample-size figure is a planning illustration, not observed power and not evidence that the trial had adequate or inadequate power. The record does not report the trial's own sample-size justification or the observed-effect value used for the illustrations. No planning result should be read as an observed trial outcome.

The record says time-to-event planning tables give total events, while other planning tables give participants per arm. The primary outcome is continuous, so the stated convention for non-time-to-event planning illustrations is participants per arm. These assumptions do not establish the actual allocation or the number analyzed in any group. They also do not replace a trial-specific statistical plan.

Why should estimates be read with their uncertainty?

General statistical interpretation separates effect size, precision, and compatibility with a model. A small estimated contrast can be precise or uncertain; a larger estimate can also be uncertain. A confidence interval helps show that uncertainty, while a p-value alone does not express the range of plausible effect sizes. Clinical importance is a further question and cannot be determined from a p-value alone. For this trial, the record does not report the effect estimates or uncertainty measures needed for those assessments. The appropriate interpretation is therefore limited to the design and outcome definitions that are recorded, rather than an inferred treatment effect.

10. Multiplicity, Missing Data and Analysis Populations

The trial describes three injection groups and more than one outcome measure. The brief summary also states hypotheses concerning pain, patient satisfaction, and function, while the registered primary outcome is pain VAS and DASH is listed as a secondary outcome. When a study evaluates multiple groups, outcomes, time points, or contrasts, multiplicity can increase the chance of at least one apparently notable finding. In general, statistical plans may identify a primary contrast or use an adjustment strategy to address this issue. The registry record does not report whether multiplicity adjustments were planned or used, which comparisons were prioritized, or how the satisfaction hypothesis was measured.

The primary outcome specifies baseline and 26 weeks. The record does not describe whether other time points were analyzed, whether the primary comparison concerned follow-up scores or change from baseline, or how multiple comparisons among the three groups were handled. These details matter because a result depends on the contrast and analysis chosen. No analysis results are reported in the registry record, so multiplicity cannot be evaluated through reported estimates or tests.

Missing-data handling is also not reported. The primary-outcome population is described as patients who completed follow-up through 26 weeks, but the record does not state how many completed it, why other participants may not have contributed, or whether any imputation or sensitivity analyses were conducted. Restricting analysis to completers can affect interpretation if completion is related to outcomes or treatment assignment; this is a general concern, not a claim that such bias occurred in this trial.

The record does not identify an intention-to-treat population, a per-protocol population, or another analysis set. It also does not describe protocol deviations, exclusions, or the statistical plan. The registry lists zero analyses, leaving the intended and performed analytical procedures unreported in the available record.

11. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: fall--hand injury (1.5%), emergency cholecystecomy (1.5%), mitral valve surgery (1.5%).

The safety entries distinguish serious adverse events from other adverse events. For bupivacaine, the registry reports 1 serious adverse event among 66 at risk and 2 other adverse events among 66 at risk. For triamcinolone, it reports 0 serious adverse events among 68 at risk and 10 other adverse events among 68 at risk. For Hylan G-F 20, it reports 2 serious adverse events among 66 at risk and 3 other adverse events among 66 at risk. These are the registry's group-specific counts and denominators; they are not a statistical comparison.

The record lists Fall--hand injury, Emergency Cholecystecomy, and Mitral Valve Surgery among the top serious-event terms, each with 1.5%. It does not provide enough detail to link each term to a specific group or explain whether the terms represent all serious events. Death counts are not reported in the registry record.

In general, adverse-event counts describe events recorded during a study, but interpretation also depends on definitions, follow-up, event timing, ascertainment, and whether events were considered related to an intervention. Those details and adjusted comparisons are not reported. The counts should not be treated as proof of causation or as a complete comparative safety assessment.

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

The record establishes that a randomized, triple-masked, parallel-group phase 3 trial was registered for thumb osteoarthritis, comparing hyaluronan, corticosteroid, and local anesthetic injections. It identifies the primary measure as pain intensity on a 0-to-100 VAS, with 100 defined as severe pain, assessed at baseline and 26 weeks. It also records DASH as a secondary outcome and reports selected adverse-event counts.

Those details do not establish how much pain changed, whether groups differed, or how precisely a difference was estimated. The record contains no primary-outcome group summaries, treatment contrasts, confidence intervals, or p-values. It does not report results for the stated hypotheses about pain relief, satisfaction, function, or baseline function. Accordingly, no conclusion about comparative effectiveness can be drawn from the registry entries.

The safety counts are descriptive entries. They do not by themselves show whether an event was caused by an injection, whether groups differed beyond chance, or how safety compares over a longer period. The record does not report death counts or a complete event narrative.

More generally, a completed trial is not the same as a fully reported trial result. Design information can clarify what investigators intended to study, while a statistical conclusion requires outcome data and methods. The registry record does not report the statistical plan, missing-data approach, or analysis populations. These absences limit what can be inferred; they are not evidence of no effect, equal effects, or a failed analysis.

The study's stated question remains scientifically interpretable: it sought to compare injections for pain and other outcomes in thumb CMC osteoarthritis. But the recorded information supports description of that question and the trial's structure, not a verdict about which group had better outcomes. Any stronger conclusion would require results and analytic details that are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly stated comparative question and the limited outcome reporting in the registry record. The design identifies three randomized injection groups, a primary pain scale, and a follow-up time. Those features define the intended comparison. Yet the record does not report the group-level outcome summaries or analyses needed to estimate the treatment contrasts. This illustrates why design details and results are distinct parts of evidence.

The primary outcome is a continuous measure summarized by a mean and standard deviation. Such summaries can describe central tendency and variability, but interpretation of a treatment comparison also requires an effect estimate and uncertainty. Without those, readers cannot distinguish a precise small contrast from a highly uncertain estimate, or assess whether a result is compatible with a range of clinically relevant effects. Statistical significance, if reported, would not by itself establish clinical importance.

The trial also raises ordinary questions about analysis choices: whether comparison concerns follow-up scores or change from baseline, how the three groups are contrasted, and how missing 26-week outcomes are handled. These are not details to assume. The record does not report them, nor does it report whether multiplicity was addressed across outcomes or comparisons.

Safety counts provide some descriptive information but do not fill the gap in primary-outcome evidence. They require careful interpretation in light of definitions, follow-up, event ascertainment, and uncertainty. The record gives counts and selected terms but not a complete comparative analysis.

For biostatisticians and clinical researchers, the practical statistical lesson is to separate what the trial was designed to ask from what the registry documents as observed. The former is described; the latter is incomplete for the primary endpoint. Transparency about this distinction prevents hypotheses, design features, and planning assumptions from being mistaken for trial findings.

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 limitation for interpretation is that the registry record does not report primary-outcome results. It gives the pain VAS definition, summary type, dispersion measure, timing, and follow-up population, but no group means, standard deviations, changes, contrasts, confidence intervals, or p-values. Consequently, the magnitude, direction, and precision of the primary comparison are unavailable.

The record identifies the primary-outcome population as patients who completed follow-up through 26 weeks but does not report the size of that population or how it relates to enrollment. It does not describe the amount or reasons for missing follow-up, the missing-data method, or sensitivity analyses. The analysis populations and handling of protocol deviations are also not reported in the registry record.

Key design and analysis details are absent. The record does not specify the masked roles, randomization sequence method, allocation concealment, planned primary contrast, model, covariate adjustment, or multiplicity strategy. It does not report the trial's sample-size justification or identify any interim analyses or stopping procedures. The planning assumptions described in the record are illustrations, not the trial's own design justification.

The outcome description is limited. DASH is listed as a secondary measure, but its results and full timing are not included in the record details. Satisfaction is part of the stated hypotheses, but a corresponding measure is not described. The registry reports zero analyses, so no statistical analysis results are available to clarify these questions.

Safety information is also incomplete for comparative interpretation. Counts and selected serious-event terms are listed, but event-level context, causal assessment, and death counts are not reported in the registry record. These limitations constrain conclusions from the record; they do not establish that the trial lacked additional information elsewhere.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of Hyaluronan for the Treatment of Osteoarthritis in the Thumb — NCT00398866.
• Registry record last updated 2017-07-07; status last verified 2017-07.
• Results first posted 2017-07-07.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

The record describes a completed phase 3, randomized, triple-masked, parallel-group trial of injections for osteoarthritis at the base of the thumb. Enrollment is listed as 200. The sponsor is Hospital for Special Surgery, New York; the recorded study start is 2006-08 and primary completion is 2013-03.

The groups received bupivacaine local anesthetic, triamcinolone corticosteroid (Kenalog 40 mg), or Synvisc (Hylan G-F 20). The primary outcome is mean pain VAS at baseline and 26 weeks, with standard deviation as the dispersion measure and a population of patients completing 26-week follow-up. DASH is listed as a secondary outcome.

Selected serious and other adverse-event counts are reported by group. The registry record does not report primary-outcome estimates, comparative analyses, confidence intervals, p-values, analysis populations, or missing-data methods. Thus, it describes the trial question and design but does not establish comparative outcome results.