Role of Bone in Knee Osteoarthritis (OA): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Role of Bone in Knee Osteoarthritis (OA) (NCT00850538), a registered phase not stated study. The primary outcome is Number of Participants With Viable Specimens for Genetic Analysis.

2. Clinical Question

3. Trial Design

The record for NCT00850538, titled “Role of Bone in Knee Osteoarthritis (OA),” describes a study of damaged knee tissues and their protein and gene expression. Its official title is “The Role of Bone and Its Measurement in Knee Osteoarthritis.” The listed condition is osteoarthritis of the knee, and the sponsor is The New England Baptist Hospital.

The study summary describes MRI before total knee replacement to identify the location of bone marrow lesions. It also describes using tendon, ligament and meniscus specimens normally discarded from total joint replacements for live-cell harvest and analyses of tissue or cultured cells. MRI and primary total knee replacement are the listed interventions. The primary outcome concerns the number of participants with viable specimens for genetic analysis, with tissue collection at surgery as its timeframe.

The registry records enrollment of 101 and gives the study dates as 2008-07 for start and 2013-04 for primary completion. Its status is completed. These registry entries describe the study record; they do not establish how many participants contributed usable specimens or were included in an outcome analysis.

The registry does not describe a randomized comparison. It states that allocation was not stated and that the arms are not a like-for-like control comparison. The record does not report treatment groups, a comparison group, or a statistical analysis of clinical outcomes. Details such as eligibility criteria, recruitment procedures, specimen-handling protocols and the criteria used to classify specimens as viable are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Viable Specimens for Genetic Analysis, measured over Tissue samples collected at time of surgery.

The primary endpoint is the number of participants with viable specimens for genetic analysis. It concerns whether tissue collected during surgery could be used for the stated genetic-analysis purpose. The timeframe is tissue samples collected at the time of surgery.

This kind of endpoint can describe whether a planned laboratory procedure yields specimens suitable for subsequent work. In general, reporting specimen viability can help readers understand the practical availability of material for genetic analysis. It is not itself a measure of symptom change, joint function, disease progression or the comparative effect of a treatment.

The record does not define what counted as “viable,” describe a laboratory threshold, or state whether viability was assessed for each specimen, each tissue type or each participant. It also does not report the observed number of participants meeting the endpoint. The endpoint title therefore identifies the intended count, but the registry record does not provide enough detail to reconstruct its operational definition or result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a count outcome: the number of participants with viable specimens for genetic analysis. It does not report an analysis estimate, a comparison, or uncertainty around the endpoint. The statistical concepts below explain how such information is ordinarily interpreted; they are general explanations, not descriptions of analyses confirmed in this study.

What does a count endpoint represent?

In general, a count records how many units meet a stated condition. For this endpoint, the unit named in the record is participants, and the condition is having viable specimens for genetic analysis. A count is most interpretable when the report also gives a clear denominator: for example, the number of participants whose specimens were assessed. The registry gives enrollment of 101, but does not say that all enrolled participants contributed an assessed specimen. Enrollment therefore cannot be assumed to be the endpoint denominator.

A count can be reported on its own, but understanding the frequency of an outcome usually also requires the relevant denominator. If the denominator is unknown, the count cannot be converted into a rate or proportion. No such conversion is reported, and no rate should be inferred from enrollment alone.

Why does the endpoint definition matter?

In general, a reproducible outcome requires an operational definition. For specimen viability, that could involve specified laboratory criteria and a consistent assessment procedure. The registry gives the endpoint label and collection timeframe but does not report those criteria. It also does not explain whether a participant is counted as having a viable specimen if one or more tissue samples meet the criteria, or how multiple tissues are handled. Those details affect what the count means and whether results can be compared across studies.

The study summary mentions tendon, ligament and meniscus specimens, as well as live-cell harvest and protein and gene-expression analyses. It does not state that the primary outcome separately counts viability by tissue type or explain how these activities relate to the endpoint’s classification. The endpoint should therefore be read according to its stated title, without assuming additional rules.

What can an uncertainty interval tell a reader?

In general, a confidence interval describes the range of values compatible with an estimate under a specified statistical method and its assumptions. It communicates precision as well as the estimated result. An interval cannot be interpreted without a reported estimate and a defined analysis population. Neither an estimate nor an interval for this primary outcome is reported in the registry record.

For a count or proportion, precision depends on what was measured and on the number of observations contributing to the analysis. A larger enrolled population does not automatically mean that the endpoint was observed for everyone. Missing specimens, failed processing, or absent assessments may affect the analysis denominator, but the record does not say whether any of these occurred. No missing-data method is reported.

What do the planning assumptions mean?

The record describes sample-size assumptions as a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation. It also says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a report of the trial’s design or evidence of observed power. The record does not report the trial’s own sample-size justification, the effect estimate used for the illustration, or sample-size results in the registry record for this explanation.

Those assumptions should not be read as evidence that this study had two randomized arms. The registry specifically says it was not a randomized comparison, allocation was not stated, and the arms are not a like-for-like control comparison. A planning illustration can explore how a hypothetical future comparison might be sized under chosen assumptions; it does not establish the design or analysis that was conducted in this study.

Why can over-dispersion matter?

In general, a count model may rely on assumptions about how much counts vary. Over-dispersion means the observed variability is greater than the model expects. If ignored, estimated uncertainty can be too small, making results appear more precise than they are. Whether over-dispersion is relevant depends on the outcome, the data structure and the chosen model. The registry record does not report a count model or an assessment of dispersion for this endpoint, so no such method can be attributed to this study.

What is the role of the registry analysis entry?

The record lists one outcome measure and zero analyses. The outcome listing states the intended measure; it does not, by itself, report the outcome value or an inferential test. No p-value, confidence interval, adjusted estimate or analysis population is reported in the registry record. A statistical conclusion requires the result and the method used to obtain it. In their absence, the sound interpretation is that the registry identifies the question but does not report its statistical answer.

10. Exact Estimates for Each Arm

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

R code and output

arm    <- c("Specimens")
n      <- c(60)
events <- c(14)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Specimens  60  14  23.3  13.4  36.0  14.4  35.4  14.5  35.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and zero analyses. It does not report a statistical analysis plan, identify a set of primary and secondary hypotheses, or describe any adjustment for multiple testing. The record therefore does not establish whether multiplicity was considered in the study’s analyses. The single listed outcome should not be taken as proof that no other analyses were conducted.

Missing-data handling is not reported in the registry record. In particular, the record does not state how participants without a collected specimen, with an unassessed specimen, or with a specimen that could not be classified were handled. It does not give the number assessed for the primary endpoint or an analysis denominator. The enrollment figure of 101 does not resolve these questions.

The analysis population is also not reported. There is no statement that the primary outcome was analyzed in all enrolled participants, only in those with surgery, or among those with specimens available for laboratory assessment. These groups need not be interchangeable for interpreting a specimen-based endpoint.

In general, multiplicity refers to the increased chance of false-positive findings when several hypotheses are tested. Missing-data methods address how unavailable or unobserved outcomes are treated. Both topics depend on the study’s prespecified plan and the observed data. Since the registry does not report those details, no conclusion about the procedures used or their effect on the findings is warranted.

12. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 1% reporting threshold.

The registry’s adverse-event entry labels the group “Enrolled.” It lists 60 at risk and 0 affected for serious adverse events, and 60 at risk and 0 affected for other adverse events. The record does not define the other adverse-event category or explain the assessment period, event-collection procedures or completeness of reporting.

These entries should be read as registry-reported figures, not as proof that every participant was monitored throughout the study or that no events occurred outside the reported categories. The record does not explain why the at-risk figures are as listed or how they relate to the enrollment figure. They should not be combined or used to infer an unreported denominator.

Deaths are not reported in the registry record; a missing death value should not be interpreted as zero. The record also lists no serious adverse-event terms among its top terms. Without details on definitions, observation time and reporting completeness, the adverse-event entry offers limited information about safety and does not support a broader safety conclusion.

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

The record establishes that the study was designed to investigate bone and other damaged knee tissues in the setting of knee osteoarthritis. It describes MRI before total knee replacement and collection of connective-tissue specimens at surgery for live-cell, protein-expression and gene-expression work. The primary outcome focuses on whether participants had viable specimens for genetic analysis.

The outcome result itself is not reported in the registry record. The study’s enrollment of 101 does not show how many participants had viable specimens, because the endpoint count and its denominator are absent. The record also does not provide a confidence interval or other measure of statistical uncertainty. Accordingly, the posted information cannot quantify specimen availability or precision.

This is not a randomized treatment comparison in the registry description. Allocation is not stated, and the arms are not described as like-for-like controls. The record therefore does not provide a basis for attributing differences in clinical outcomes to a treatment. Its stated primary question concerns specimen viability, not whether an intervention changes osteoarthritis or improves a patient outcome.

In general, a completed study status indicates a registry status, not that every planned outcome result is present in the registry. Here, the status is completed, but the primary result and analysis details are not reported. The description can clarify the research aim and procedures recorded, while leaving the main numerical outcome unanswered.

The appropriate interpretation is narrow: the registry identifies an intended tissue-based investigation and a specimen-viability endpoint, alongside limited adverse-event figures. It does not establish the endpoint result, the completeness of outcome ascertainment, or a clinical treatment effect. No conclusion about medical care should be drawn from these registry entries alone.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary question is about whether biological specimens are available for genetic analysis, rather than about a comparative clinical outcome. Such feasibility-oriented questions require careful attention to what is counted, which participants contribute to the count, and how “viable” is defined. The registry names the endpoint and its surgical collection timeframe, but does not report the operational criteria or observed result.

The distinction between enrollment and endpoint assessment is central. Enrollment is recorded as 101, while the primary outcome is a participant count based on viable specimens. Without the number assessed and the endpoint count, readers cannot determine the frequency of successful specimen availability. This illustrates why a recruitment figure cannot substitute for an endpoint denominator.

The record also shows why design labels matter. It states that this was not a randomized comparison and that allocation was not stated. Although planning assumptions refer to equal allocation between two arms, those assumptions do not define the actual study design. Planning calculations are conditional on their assumptions and should not be confused with an observed result or a completed trial analysis.

Finally, the registry’s limited outcome and safety reporting separates a study’s stated purpose from the evidence needed to evaluate its result. An endpoint description can indicate what investigators intended to measure, but interpretation also depends on the measured value, analysis population, missing-data handling and uncertainty. These elements are not reported for the primary outcome in this record.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record leaves important details about the primary endpoint unresolved. It does not define the criteria for specimen viability, specify how multiple tissue specimens relate to a participant-level count, or report how viability was assessed. The endpoint’s stated timeframe is tissue collection at surgery, but the record does not describe subsequent laboratory assessment procedures or timing.

The primary outcome value and its denominator are not reported. Although enrollment is listed as 101, the record does not state how many participants underwent the relevant collection, had specimens assessed, or contributed to an analysis. It also does not describe missing, unusable or unclassified specimens. These gaps prevent calculation or interpretation of an endpoint rate.

The record describes MRI to identify bone marrow lesions and collection of tendon, ligament and meniscus specimens, but does not report how imaging findings were linked to tissue analyses or to the primary endpoint. It does not give an analysis plan, statistical model, uncertainty estimate, or analysis population. The registry lists no analyses.

There is no randomized comparison described, and allocation is not stated. The record warns that the arms are not a like-for-like control comparison. The adverse-event entry has limited contextual information, and deaths are not reported. These registry limitations do not establish that details or analyses were absent from all study materials; they mean those details are not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Role of Bone in Knee Osteoarthritis (OA) — NCT00850538.
• Registry record last updated 2015-12-04; status last verified 2015-11.
• Results first posted 2015-12-04.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT00850538 is a completed study of knee osteoarthritis sponsored by The New England Baptist Hospital. The registry records enrollment of 101, a start date of 2008-07 and primary completion in 2013-04. Its summary describes MRI before total knee replacement and tissue collection at surgery for live-cell, protein-expression and gene-expression work.

The primary outcome is the number of participants with viable specimens for genetic analysis. The registry record does not report the observed outcome, its denominator, an analysis plan or statistical analyses. It describes no randomized comparison and says allocation was not stated. Serious and other adverse-event entries each list 60 at risk and 0 affected; deaths are not reported.