A Multicenter Study to Evaluate Functional Outcome After Knee Replacement: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Multicenter Study to Evaluate Functional Outcome After Knee Replacement (NCT02494544), a non-randomized na study. The primary outcome is Functional Activities Subscale Score Within the Knee Society Score (KSS) Measure.

2. Clinical Question

The outcome is a continuous score intended to reflect functional knee health. The registry describes a comparison of functional testing between iTotal and off-the-shelf systems, alongside patient questionnaires. It also lists patient satisfaction and major procedure-related or device-related complications, including revision rates, as secondary outcomes.

This is a comparison of outcomes in groups formed according to the implant received, not a randomized treatment comparison. The registry explicitly notes that the arms are not a like-for-like control comparison. Differences between groups could reflect factors other than the implant, and the record does not report enough outcome information to determine the direction or size of any functional-score difference.

3. Trial Design

This was a prospective, multicenter study of functional outcomes after knee replacement for osteoarthritis. The registry lists a planned enrollment of 215 and describes consecutive enrollment by implant. Participants were grouped according to whether they underwent surgery with a ConforMIS iTotal system or an off-the-shelf system. The listed off-the-shelf arms include DePuy, Zimmer, Biomet, Smith & Nephew, and Stryker implants.

The allocation is recorded as non-randomized, with a sequential model and single masking. What was masked, and to whom, is not reported in the registry record. Because treatment assignment was not randomized, the comparison may reflect differences in the patients, clinical circumstances, or other factors associated with the implant selected. The registry itself cautions that the arms are not a like-for-like control comparison.

The primary outcome was the KSS Total Functional Activities subscale score at 1 year. The registry describes functional testing and questionnaires. It also lists patient satisfaction and major procedure-related or device-related complications, including revision rates, as secondary outcomes. The exact measurement schedule for those secondary outcomes is not reported in the registry record.

The study status is terminated. The record gives a start date of 2015-07-01 and a primary completion date of 2022-11-16. The reason for termination is not reported in the registry record. The record does not report the number enrolled in each implant group, the number completing follow-up, or whether the primary outcome was collected for all enrolled participants. A phase is listed as not applicable.

The registry record does not report the protocol’s sample-size justification, detailed statistical analysis plan, interim analyses, or the reason the study ended. These omissions limit assessment of how the study’s planned analyses relate to the outcomes ultimately collected and reported.

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

Analysis population for the primary outcome, as defined in the registry: Patients that met inclusion criteria and had KSS Total Functional Activities Score.

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: Our analysis expected a broader range of off the shelf implants, but no included patients received Biomet or Smith \& Nephew Total Knee Replacements.

Only the first 6 of 7 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Functional Activities Subscale Score Within the Knee Society Score (KSS) Measure, measured over 1 year.

The primary endpoint is the Functional Activities subscale within the Knee Society Score (KSS), assessed at 1 year. The registry describes the endpoint as a total score made up of walking and standing, standard activities, advanced activities, and sports or recreational activities. It also notes that deductions can be made for mobility limitations, such as needing an ambulatory device. The scoring range is 0-100, with higher scores indicating better knee function.

This is a continuous measure, and the specified summary is the mean with standard deviation. A mean describes the group’s average score; a standard deviation describes how dispersed individual scores are around that average. Both can help characterize functional outcomes, but neither alone establishes whether groups differ reliably or whether any difference is clinically important.

The endpoint is used because it captures function through a combination of reported activities and mobility-related limitations, rather than focusing only on a single symptom or task. The registry states that the study compares functional testing between the iTotal and off-the-shelf systems. However, it does not report the primary endpoint’s group means, standard deviations, group sizes for this outcome, or a between-group estimate. The size and precision of the functional-score comparison therefore cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: a score on the KSS Functional Activities subscale. The registry specifies that it is summarized by a mean and standard deviation. The mean represents the average score in a group, while the standard deviation describes variation among scores. These summaries convey different information: groups can have similar means but different variability, or different means with substantial overlap in individual scores.

What does a between-group estimate tell the reader?

For a continuous outcome, an unadjusted comparison commonly expresses the difference between group means. The estimate describes the size and direction of the observed contrast; uncertainty around it indicates how precisely the contrast has been estimated. A confidence interval is a range produced by a statistical procedure that, under its assumptions, reflects uncertainty about the underlying comparison. It is not a guarantee that the true value lies within any particular reported interval. The registry record does not report a mean difference or confidence interval for the primary outcome, so those features cannot be interpreted for this study.

Why does non-randomized allocation matter?

In a randomized study, the assignment process is designed to make groups comparable on average with respect to measured and unmeasured characteristics. Here, allocation is recorded as non-randomized, and enrollment was consecutive by implant. Implant groups may differ at baseline or in treatment circumstances. If characteristics related to function also differ across groups, an observed score contrast could reflect those differences as well as the implant received. Statistical adjustment can address measured factors when appropriately planned and conducted, but cannot automatically remove bias from unmeasured factors. Whether an adjusted analysis was performed, and which variables it included, are not reported in the registry record.

What is the role of standard deviation?

Standard deviation describes the spread of individual observations around a group mean, in the same units as the score. It is not the uncertainty in the mean itself and should not be read as a confidence interval. The uncertainty of a mean depends on both the observed variability and the number of participants contributing data. The registry lists the intended dispersion measure but does not report the primary outcome’s group standard deviations or endpoint-specific sample sizes.

How should planning illustrations be read?

General statistical explanation: a sample-size planning calculation asks how many participants might be needed under specified assumptions to detect an effect of a chosen size at a chosen significance level and power. It is a planning exercise, not a measure of the probability that an observed result is true. A planning illustration based on an observed effect is particularly dependent on that effect estimate and may not represent the trial’s original design. The registry record does not report its own sample-size justification. Any planning illustrations should therefore be distinguished from the enrolled sample and from evidence about the trial’s actual statistical power.

Why can over-dispersion matter?

General statistical explanation: over-dispersion occurs when observed variability is greater than a model assumes. If a model understates variability, standard errors can be too small and uncertainty intervals too narrow. Whether over-dispersion is relevant depends on the outcome and analysis model. The primary endpoint is a continuous score, and the registry record does not identify a statistical model or report diagnostics. It is therefore not possible to say whether over-dispersion was assessed or relevant to the analyses.

What can be concluded from the reported analysis information?

The registry lists 3 outcome measures and 0 outcome analyses. It specifies the primary endpoint’s scale, summary measure, and 1-year timeframe, but does not report an inferential method, a prespecified analysis population, an adjustment strategy, or results for the primary comparison. The actual statistical analysis plan is not reported in the registry record. Without those details and the endpoint results, readers cannot evaluate whether the analysis followed a prespecified plan, how uncertainty was handled, or whether the comparison accounts for the non-randomized design.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures, including the primary functional activity score and secondary outcomes for patient satisfaction and major procedure-related or device-related complications. Testing multiple outcomes can raise multiplicity concerns: when many hypotheses are evaluated, the chance of at least one apparently unusual result can increase. This is a general statistical issue, not a claim about what occurred in this study. The registry record does not report a multiplicity strategy, such as a hierarchy of outcomes or an adjustment to account for multiple testing.

The record lists 0 outcome analyses. It does not report primary or secondary outcome estimates, hypothesis tests, or confidence intervals. It is therefore not possible to assess which outcomes were analyzed, whether all planned comparisons were reported, or how any multiple comparisons were handled. The protocol’s analysis plan is not reported in the registry record.

The study population for the primary endpoint is described as patients meeting inclusion criteria and having a KSS Total Functional Activities Score. However, the record does not report the number of eligible patients, the number with a score at 1 year, or the analysis population used for an outcome comparison. It also does not describe how missing scores were handled, whether participants were excluded from analyses, or whether sensitivity analyses were conducted. The extent and potential effect of missing data therefore cannot be assessed.

These gaps matter in a non-randomized study, where both group composition and availability of follow-up measurements may affect interpretation. The registry record does not report whether missingness differed between implant groups or whether any method was used to address it.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: sas (21.4%).

The registry reports serious adverse event figures by implant group. For the ConforMIS iTotal group, it lists 13 serious adverse events among 81 at risk; for DePuy, 6 among 28; for Zimmer, 2 among 19; and for Stryker, 0 among 19. It lists no participants at risk and no serious adverse events for the Biomet and Smith & Nephew groups. The registry reports 0 deaths in each listed group.

These are descriptive registry counts, not a randomized safety comparison. The groups differ in size, and the study was non-randomized. The record does not clarify in the displayed information whether the affected counts represent participants or events, nor does it report follow-up duration for these safety figures. The Biomet and Smith & Nephew entries, with no participants at risk, do not provide evidence about safety in those groups.

The leading serious adverse event term is listed as “SAS” at 21.4%. The meaning of “SAS,” its denominator, and the method used to identify a leading term are not reported in the registry record. These figures should be read as recorded safety information, not as proof that one implant is safer or less safe than another.

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

The registry record describes a prospective, multicenter study comparing functional outcomes after ConforMIS iTotal and off-the-shelf knee replacement. It identifies a KSS Functional Activities score at 1 year as the primary endpoint and explains that higher scores indicate better knee function. It also documents a planned enrollment of 215 and lists secondary outcomes relating to satisfaction and complications.

What the record does not provide is the primary endpoint result. There are no reported group means, standard deviations, between-group estimates, or confidence intervals. The record therefore does not establish whether scores were higher in one group, how large any difference was, or how precisely a difference was estimated. It also does not report results for the listed secondary outcomes.

The non-randomized design is important: implant groups were formed according to the implant received, rather than randomized assignment. Any observed contrast could be influenced by differences between the groups apart from the implant. The registry explicitly warns that the arms are not a like-for-like control comparison. Without reported adjustment methods and group characteristics, the extent of that concern cannot be quantified.

Likewise, the study’s terminated status does not by itself explain why it ended or what happened to outcome collection. The reason for termination, the number of participants with 1-year scores, and the handling of missing data are not reported in the registry record. These gaps prevent a complete assessment of the analysis.

The appropriate conclusion is narrow: the record specifies a comparison and outcome, but does not post the functional results needed to judge the observed comparison. It cannot be used to conclude that either implant improves function, performs worse, or is equivalent to the other. Absence of a posted result is not evidence of no difference.

13. Why This Trial Matters Statistically

This study is statistically notable because its registry description combines a patient-reported and activity-based functional outcome with a non-randomized comparison across several implant systems. The primary score is a continuous measure with a defined range and higher values indicating better knee function. That makes the endpoint interpretable in principle, but interpretation still depends on the group summaries, the comparison estimate, and its uncertainty.

The design illustrates a central issue in clinical research: an outcome difference between groups is not automatically an effect of treatment when allocation is not randomized. Consecutive enrollment by implant may reflect how patients came to receive a particular system. The registry itself cautions that the groups are not like-for-like controls. This makes clear reporting of group characteristics and analysis methods important, yet those details are not reported in the registry record.

The record also demonstrates why registration information and outcome reporting serve different purposes. A registry entry can identify intended endpoints, follow-up timing, and study status without providing analyzed results. Here, 0 outcome analyses are listed, so the registered question cannot be answered from the posted outcome data.

Safety counts also need context. Unequal group sizes, non-randomized allocation, and unreported details about event definitions and follow-up limit direct comparisons. The presence of counts is useful descriptive information, but it does not settle comparative safety.

For readers evaluating clinical evidence, the key statistical lesson is to distinguish the research question from evidence answering it. A defined endpoint and a planned comparison do not substitute for transparent results, uncertainty estimates, and analysis details. Those elements are not reported in the registry record for the primary functional outcome.

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.

Several limitations specific to this study restrict interpretation. First, allocation was non-randomized and participants were enrolled consecutively by implant. The registry explicitly states that the arms are not a like-for-like control comparison, so differences in patient or treatment characteristics could affect group outcomes. The record does not report enough information to evaluate or adjust for these differences.

Second, the registry record does not report the primary KSS Functional Activities score results, despite identifying the endpoint and its 1-year timeframe. Group means, standard deviations, and a comparison estimate are absent, as are confidence intervals. The functional outcome therefore cannot be characterized for either group from the registry record.

Third, the record lists 0 outcome analyses and does not report the analysis population, endpoint-specific group sizes, missing-data methods, or a detailed statistical plan. It is not possible to assess whether available scores represent all enrolled patients or how incomplete follow-up might affect estimates. The reason for the terminated status is also not reported in the registry record.

Fourth, although the registry lists secondary outcomes, their results are not reported. The safety entries include groups with no participants at risk, and the record does not clarify all details needed to interpret event counts or the leading term “SAS.”

Finally, the registry does not report its sample-size justification, interim analyses, or a multiplicity strategy. The planned enrollment alone cannot establish whether the study was adequately sized for its primary question. Together, these reporting gaps mean that the study’s intended comparison is clearer than its evidential result.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Multicenter Study to Evaluate Functional Outcome After Knee Replacement — NCT02494544.
• Registry record last updated 2025-11-21; status last verified 2025-11.
• Results first posted 2025-10-08.
• 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 registry record describes a prospective, multicenter, non-randomized study of functional outcomes after knee replacement for osteoarthritis. Patients were to be consecutively enrolled by implant, with the comparison between ConforMIS iTotal and off-the-shelf systems. Planned enrollment was 215, and the study is listed as terminated.

The primary outcome was the mean KSS Total Functional Activities subscale score at 1 year. The record describes the score’s activity domains and states that higher scores indicate better knee function. Patient satisfaction and major procedure-related or device-related complications were listed as secondary outcomes.

No outcome analyses are listed, and the primary functional results are not reported in the registry record. The reason for termination, analysis methods, missing-data handling, and sample-size justification are also not reported. The posted information defines the intended question but does not provide results sufficient to assess the functional comparison.