Iterative Design of Custom Dynamic Orthoses to Reduce Articular Contact Stress: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Iterative Design of Custom Dynamic Orthoses to Reduce Articular Contact Stress (NCT04562896), a randomized na study. The primary outcome is Joint Contact Stress Time Exposure (Model Estimated).

2. Clinical Question

3. Trial Design

The registry describes a randomized, single-masked crossover study of custom carbon fiber dynamic orthoses. The study was sponsored by the University of Iowa and is listed as completed. Its enrollment is recorded as 22. The registry gives a start date of 2020-01-08 and a primary completion date of 2023-10-05. The phase is listed as not applicable.

Participants were evaluated without a CDO or with one of three design variants: CDO-A, CDO-B or CDO-C. The study description says that brace geometry was varied to investigate its influence on forces experienced by ankle cartilage. The primary endpoint used participant-specific musculoskeletal models to estimate ankle joint contact stress time exposure during gait.

A crossover design generally means that participants receive or are evaluated under multiple conditions, allowing comparisons within the same person. In general, such comparisons can account for stable differences between people, but they also require attention to condition order, changes over time and possible carryover. The order of conditions, period structure, washout procedures and methods for handling these design features are not reported in the registry record. The record labels masking as single, but does not identify who was masked.

Although the registry describes the overall study as a crossover, the primary outcome description says that peak stress was calculated only for participants in Group 1. Posted primary summaries are available for Group 1 under NoCDO, CDO-A, CDO-B and CDO-C. The other listed group-condition rows have no reported primary outcome values. The record does not explain the relationship between those groups and the primary analysis or why only Group 1 contributed to that endpoint.

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.

Only the first 6 of 18 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Peak joint contact stress time exposure was only calculated for participants in group 1.

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: Some randomization options (ex. Group 1: NoCDO, CDOB, CDOC, CDOA) had no participants assigned to them, resulting in an overall number of baseline participants equaling zero.

Only the first 6 of 19 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Joint Contact Stress Time Exposure (Model Estimated), measured over Baseline.

The primary endpoint is Joint Contact Stress Time Exposure, model estimated and reported as a mean with standard deviation at baseline. It represents peak joint contact stress time exposure acting on the tibia during the gait cycle. The registry states that it was estimated with a participant-specific musculoskeletal model and expressed in MPa-s/gait cycle.

This is a biomechanical endpoint rather than a direct measure of later arthritis or a patient-reported symptom. It was selected to quantify forces relevant to the study’s stated question: whether changing brace geometry influences ankle cartilage loading. The registry describes lower peak contact stress time exposure as a better outcome. That direction describes how the measure is interpreted; it does not establish that a difference in the modeled measure changes a person’s health outcome.

For Group 1, the posted mean and standard deviation are 4.44 and 2.8 for NoCDO, 3.97 and 3.33 for CDO-A, 4.08 and 2.96 for CDO-B, and 4.25 and 2.94 for CDO-C. The associated reported sample size is 6.0 for each condition. These are descriptive summaries. The registry does not report a confidence interval or an inferential test for the primary outcome.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a numerical measure of model-estimated joint contact stress time exposure. The registry reports the mean and standard deviation for each posted Group 1 condition. In general, a mean describes the central value of a set of measurements, while a standard deviation describes their spread around that mean. These are useful descriptive statistics, but they do not by themselves quantify uncertainty in a comparison between conditions.

What would a crossover analysis need to account for?

In general, crossover data are different from data in which separate participants receive separate conditions. When a participant contributes results under more than one condition, measurements from that person are related. An analysis should account for this within-person dependence rather than treating every condition summary as independent. Pairing can improve the precision of a comparison when the same person’s measurements are correlated, but that benefit depends on the actual paired data and an appropriate analysis.

The registry labels this study randomized and crossover, but it does not report condition sequences, period details, washout procedures or a statistical model for the primary endpoint. It also does not report participant-level observations or within-person contrasts. The posted means and standard deviations cannot reveal the correlation between measurements from the same person. Accordingly, a crossover-specific treatment contrast cannot be recovered from the marginal summaries alone.

How should uncertainty be understood?

In general, a confidence interval gives a range of values reasonably compatible with the data under the assumptions of the analysis. For this study, no confidence interval for a primary contrast is reported in the registry record. Nor are a test statistic or p-value reported for the primary outcome. Without an inferential analysis, readers cannot determine how precisely the condition differences were estimated or how strongly the observed summaries distinguish among the device conditions.

The standard deviations reported for the conditions characterize variation in the endpoint values, not uncertainty in the estimated means or contrasts. The difference between those concepts matters: a spread measure describes the observed distribution, whereas uncertainty in a treatment contrast depends on the comparison design and the information used by the analysis. In a crossover study, that includes the paired structure, which is not recoverable from separate means and standard deviations.

What is the role of the statistical plan?

The registry lists zero analysis entries. The primary analysis method, adjustment variables, handling of period or sequence effects, and rules for selecting the analysis population are not reported in the registry record. The absence of a posted analysis means the descriptive summaries should not be presented as if they were results from a prespecified inferential model. It also prevents an assessment of whether the planned analysis matched the crossover structure.

The registry’s sample-size assumptions describe planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between the two arms and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence of achieved power, and the registry record does not report a trial-specific sample-size justification. A planning illustration based on an observed effect cannot establish the precision or reliability of the trial’s actual results.

In general, over-dispersion means that observed variability is greater than a statistical model expects. It is more commonly a concern for count outcomes than for this continuous primary endpoint, but the broader principle is relevant: if a model understates variability, uncertainty can be understated as well. The registry does not report an over-dispersion assessment or a primary-outcome model, so no claim about either can be made for this study.

The endpoint is generated using a participant-specific musculoskeletal model. In general, modeling can make it possible to estimate biomechanical quantities that are not directly observed in the same way as a simple physical measurement. The resulting estimate also depends on model assumptions and inputs. Model specification, validation, and uncertainty propagation are not reported in the registry record. The posted mean and standard deviation therefore describe the reported endpoint values, but do not capture every possible source of uncertainty in the modeling process.

For context, the record names secondary outcomes including model-estimated peak soleus and gastrocnemius muscle force, ankle range of motion, ankle moment and power, the Four Square Step Test, the Sit to Stand 5 Times measure, and the Orthotics Prosthetics Users' Survey. The posted record states 10 secondary outcomes and 34 outcome measures. A statistical analysis would need to define how these outcomes relate to the primary question and how multiple comparisons are handled. The corresponding multiplicity plan is not reported in the registry record.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Group 1: NoCDO", "Group 1: CDOA", "Group 1: CDOB", "Group 1: CDOC")
n   <- c(6, 6, 6, 6)
m   <- c(4.44, 3.97, 4.08, 4.25)
sp  <- c(2.8, 3.33, 2.96, 2.94)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Group 1: NoCDO  6  4.440  2.800  1.502  7.378
CARM  Group 1: CDOA  6  3.970  3.330  0.475  7.465
CARM  Group 1: CDOB  6  4.080  2.960  0.974  7.186
CARM  Group 1: CDOC  6  4.250  2.940  1.165  7.335

11. Multiplicity, Missing Data and Analysis Populations

The registry records 34 outcome measures and 10 posted secondary outcomes. The named secondary measures include model-estimated peak soleus muscle force, model-estimated peak gastrocnemius muscle force, ankle range of motion, peak ankle moment, peak ankle power, the Four Square Step Test (4SST), Sit to Stand 5 Times (STS5), and the Orthotics Prosthetics Users' Survey (OPUS). Multiple outcomes and several orthosis conditions can create multiple opportunities to observe an apparently notable result. In general, multiplicity procedures can help control the chance of false-positive findings across a defined family of tests.

The statistical plan for defining comparison families, adjusting for multiple comparisons or prioritizing secondary outcomes is not reported in the registry record. No primary-outcome analysis is listed, and the record provides no inferential tests for the secondary outcomes in the registry record for this trial. As a result, no conclusion about multiplicity-adjusted evidence can be made.

Missing-data methods are also not reported in the registry record. The primary outcome description limits calculation to Group 1, but does not explain the absence of primary values in the other group-condition rows. The record does not describe whether observations were unavailable, excluded, or considered not estimable, nor does it state how any missing measurements were handled in an analysis. The reported Group 1 sample size is 6.0 for each posted condition; that alone does not explain the missing group rows or establish how many participants contributed paired data.

The record does not report analysis-population definitions, such as criteria for inclusion in the primary analysis or how randomized participants were treated if they did not complete all conditions. The actual analysis population and the handling of incomplete crossover data are therefore not reported in the registry record. These omissions limit assessment of whether the posted summaries represent the randomized population, the participants with available measurements, or another defined subset.

12. 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.

The registry reports zero serious adverse events, zero other adverse events and zero deaths for every listed group-condition entry. It gives the number at risk as 7 for each Group 1 condition, 6 for each Group 2 condition and 9 for each Group 3 condition. The serious adverse event terms list is empty.

These figures describe the adverse-event counts posted in the registry. They should not be read as proof that no adverse effects are possible or that the device conditions are risk-free. A zero count means no events were recorded in the reported entries; it does not establish that an event could not occur or quantify the uncertainty around its frequency.

The adverse-event numbers at risk do not match the reported primary-outcome sample size for Group 1, which is 6.0 per condition. The registry record does not explain the difference between the safety and primary-outcome counts, or how the at-risk populations were defined. These measures may refer to different analysis or reporting populations, but the reason is not reported in the registry record. No further conclusions about safety comparisons can be drawn from the posted counts alone.

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

The results establish that the registry posted baseline descriptive summaries for model-estimated joint contact stress time exposure in Group 1 under NoCDO, CDO-A, CDO-B and CDO-C. The recorded means are 4.44, 3.97, 4.08 and 4.25 MPa-s/gait cycle, respectively; the associated standard deviations are 2.8, 3.33, 2.96 and 2.94. The registry states that lower peak contact stress time exposure is considered better.

Those summaries do not establish that the device conditions differ. The registry does not report an inferential primary-outcome analysis, a confidence interval or a p-value. Without those results, the uncertainty in any comparison cannot be judged. The record also does not provide participant-level paired results, so the crossover comparison cannot be reconstructed from the posted group summaries.

The endpoint is a model-estimated biomechanical measure. It represents ankle joint loading during gait, not the occurrence of post-traumatic osteoarthritis or a direct measure of a later clinical outcome. The study summary describes a rationale connecting ankle forces with arthritis after fracture, but this record does not report evidence that a change in the modeled endpoint leads to a change in arthritis risk. It would therefore be inappropriate to translate the descriptive means into a claim about preventing arthritis or improving health.

Likewise, the posted adverse-event counts are not evidence that a device condition is free from risk. They record zero events in the listed entries, while the registry does not explain the safety populations or the differences between the safety counts and primary-outcome sample sizes.

In short, the record documents the study question and several descriptive endpoint values. It does not report enough statistical analysis to establish the size, precision or clinical significance of a difference among the orthosis designs and the no-device condition.

14. Why This Trial Matters Statistically

The study addresses a statistical challenge that arises when evaluating design variants of a device: the scientific question concerns how changes in geometry relate to a continuous biomechanical measure, while the design is recorded as a randomized crossover. Crossover designs can support within-person comparisons, but valid inference depends on retaining that pairing and addressing the structure of conditions over time. The registry’s posted marginal summaries do not show those within-person comparisons.

The primary endpoint is also model estimated. This makes the distinction between a measured clinical outcome and a modeled biomechanical quantity especially important. Statistical interpretation should reflect not only variation in the reported values, but also uncertainty from the analysis and, in general, the model used to estimate the endpoint. The registry reports descriptive summaries but does not report an inferential model or model-validation details.

There are multiple CDO variants, a no-device condition and a broader set of outcome measures. This creates a need for a clear analysis plan that identifies the primary comparisons and addresses multiplicity. No such plan is reported in the registry record. Without that information, selective emphasis among several comparisons cannot be assessed.

The record is therefore useful for identifying the study’s design, endpoint and posted descriptive results, while also illustrating why summaries alone do not answer the inferential question. Reporting participant-level or properly analyzed crossover contrasts, uncertainty intervals and methods for handling missing data would make the evidence easier to evaluate. Those details are not reported in the registry 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 primary-outcome summaries cover Group 1 only, according to the endpoint description. The registry does not explain why primary values are absent for the listed Group 2 and Group 3 conditions, or how the groups relate to the overall crossover design. This restricts the scope of interpretation to the posted Group 1 summaries.

The record gives means and standard deviations but no primary comparison estimates, confidence intervals or p-values. It also does not report participant-level paired measurements. Consequently, the posted summaries cannot establish the precision of differences or show whether the analysis accounted for within-participant dependence expected in a crossover design.

Details needed to assess the design and analysis are not reported in the registry record. These include condition order, period structure, washout procedures, the identity of the masked party, the primary statistical model, missing-data handling, analysis-population definitions and the multiplicity plan. No trial-specific sample-size justification is reported; the stated assumptions concern planning illustrations rather than observed power.

The endpoint depends on a participant-specific musculoskeletal model, but its specification, validation and estimation uncertainty are not reported. The primary outcome is a biomechanical surrogate measure, and the posted registry results do not connect it to later arthritis or another clinical outcome. The adverse-event entries report no events, but do not explain the populations at risk or the difference between those counts and the primary endpoint sample sizes. These limitations leave substantial uncertainty about how broadly the posted results can be interpreted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Iterative Design of Custom Dynamic Orthoses to Reduce Articular Contact Stress — NCT04562896.
• Registry record last updated 2026-01-30; status last verified 2025-04.
• Results first posted 2025-01-23.
• 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

NCT04562896 is a completed randomized, single-masked crossover study sponsored by the University of Iowa. It evaluated custom carbon fiber dynamic orthoses with three design variants and a no-device condition. The registry describes an enrollment of 22 and lists ankle fractures and ankle osteoarthritis among the study conditions.

The primary endpoint was baseline, model-estimated peak joint contact stress time exposure during gait, expressed in MPa-s/gait cycle. Results are posted only for Group 1: the means were 4.44 for NoCDO, 3.97 for CDO-A, 4.08 for CDO-B and 4.25 for CDO-C. Each condition has a reported sample size of 6.0. No inferential primary-outcome analysis is reported in the registry record.

The record also reports zero serious adverse events, zero other adverse events and zero deaths in each listed condition. Analysis methods, missing-data handling, crossover details and multiplicity procedures are not reported in the registry record.