Treadmill Training and Orthotic Use in Infants With Down Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Treadmill Training and Orthotic Use in Infants With Down Syndrome (NCT00825175), a randomized na study. The primary outcome is Pattern of Gross Motor Development.

2. Clinical Question

3. Trial Design

The study, titled Treadmill Training and Orthotic Use in Infants With Down Syndrome, is registered as NCT00825175 and sponsored by the University of Michigan. The official title describes the study as examining treadmill training and orthotic use in relation to the development of walking and upright play. The registry lists Down syndrome as the condition and the phase as NA.

The design is randomized, parallel-group, and unmasked. The two listed arms are Treadmill Training Only and Treadmill Training and Orthotic Use. Both groups received treadmill training; use of supramalleolar orthoses distinguishes the combination arm. The registry record does not report the allocation ratio, the method used to generate the random sequence, or the process used to conceal assignments.

Enrollment is recorded as 22. The registry lists the study start as 2006-03, primary completion as 2008-06, and status as completed. These details describe the registered study timeline and enrollment, not necessarily the number contributing data to every outcome. For the primary outcome, the posted arm counts are 10 for treadmill training only and 7 for treadmill training with orthotic use. The record does not explain the difference between the overall enrollment and those outcome counts.

One primary outcome measure is listed, and no secondary outcome measures are posted. The registry record does not report eligibility details, the intervention schedule or dose, follow-up procedures beyond the outcome timeframe, or a detailed protocol. It also does not report a statistical analysis plan or a sample-size justification. Those omissions limit what can be concluded about the intended conduct and analysis beyond the registered design and posted outcome values.

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: Subjects were excluded if they previously had worn foot orthoses

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: analysis was on protocol

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 Pattern of Gross Motor Development, measured over monthly; starting when child can pull to stand and ending when the test determined that the child was walking..

The primary outcome, Pattern of Gross Motor Development, measures age in months at walking development, as indicated by the Gross Motor Function Measure. The registry describes the Gross Motor Function Measure as a standardized test of gross motor development. The reported quantity is a mean, with standard deviation as the measure of spread.

The outcome was assessed monthly, starting when a child could pull to stand and ending when the test determined that the child was walking. This definition connects the endpoint to a developmental milestone while using a standardized assessment to identify the milestone. Age in months gives the result a direct time scale: the arm summaries describe the average age at which walking development was indicated by the measure.

A continuous outcome such as age can be summarized by a mean and standard deviation. The mean describes the center of the observed values, while the standard deviation describes their spread around that center. Neither alone gives the full distribution of individual ages, and a mean does not show how many participants walked at any particular age. The registry record does not report additional distributional summaries or individual participant data.

The posted mean is 28.2 months in the treadmill-training-only arm and 28.3 months in the arm combining treadmill training and orthotic use. The endpoint therefore addresses the timing of walking development as operationalized by the test; it does not directly summarize every aspect of gross motor function or upright play named in the official title.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the randomized parallel design mean?

Randomization assigns participants to study groups by chance, with the aim of making the groups comparable on average at the start of the study. It does not guarantee that every measured or unmeasured characteristic will be balanced, especially in a small study. A parallel-group design means participants are assigned to one intervention group and remain in that group for the relevant comparison, rather than receiving each intervention in sequence. The registry record identifies the study as randomized and parallel, but it does not describe the random sequence method, concealment of assignments, or allocation ratio.

The groups differ in the registered intervention components: treadmill training alone versus treadmill training combined with supramalleolar orthoses. Therefore, a comparison between these groups concerns the addition of orthotic use in the context of treadmill training. It does not isolate treadmill training from all other care, since both arms include treadmill training.

How should the continuous outcome be read?

Age at walking development is continuous and is measured in months. The registry reports a mean and standard deviation for each arm. A mean is the arithmetic average of the observed values, while a standard deviation describes how widely observations are spread around the mean. The standard deviation is not the uncertainty of the mean and is not a confidence interval. It describes participant-level variation in the recorded outcome.

Mean and standard deviation summaries can be useful when the distribution is reasonably represented by those quantities. If a distribution is strongly skewed or contains influential values, the mean may not describe a typical observation well. The registry record does not report the shape of the outcome distribution, a median, or a diagnostic assessment. The small outcome counts also mean that the summaries represent a limited set of observations; the record does not provide individual data with which to assess their distribution.

What is a group comparison estimate?

A between-group estimate would quantify the contrast in mean age between the two arms using a stated direction and analysis method. The registry does not report such an estimate, a confidence interval, or a p-value. It flags values as missing or not estimable for a two-arm comparison of this continuous endpoint. The arm-specific means and standard deviations therefore should not be mistaken for a completed inferential analysis.

In general, a confidence interval expresses the uncertainty of an estimate under the assumptions of its statistical method. A narrower interval indicates greater precision, while a wider interval indicates less precision. An interval that includes a value representing no difference would not, by itself, establish equivalence; equivalence requires a predefined margin and an analysis designed to evaluate it. No equivalence margin or such analysis is reported in the registry record.

In general, a p-value summarizes how compatible observed data are with a specified null hypothesis and model. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of an effect. Since no p-value or model is reported for the primary comparison, the posted arm summaries cannot answer an inferential question by themselves.

Why do analysis population and missingness matter?

The primary outcome population is described as analysis on protocol. In general, an analysis limited to participants who followed a protocol can differ from an analysis that retains everyone as randomized. The former may be sensitive to departures from protocol or differences in who remains evaluable. The registry record does not define the analysis-on-protocol criteria, identify exclusions, or report a separate analysis using all randomized participants.

The outcome counts are 10 and 7, whereas total enrollment is 22. These registry entries indicate that the posted endpoint summaries do not include a count matching total enrollment, but they do not explain why. Missing outcome measurements, exclusions, or other pathways cannot be distinguished from the registry information. No missing-data method, sensitivity analysis, or participant flow accounting is reported.

What can planning calculations tell the reader?

In general, a sample-size planning calculation estimates how many participants may be needed to detect a chosen effect under specified assumptions about significance level, allocation, and statistical model. Such a calculation is a planning illustration, not evidence about what the completed study observed. The registry record does not report the trial's own sample-size justification or a statistical plan. It also does not provide an estimable two-arm continuous comparison for a planning illustration based on the observed effect. No planning sample size should therefore be interpreted as a result from this trial or as observed power.

Over-dispersion is a general concern for count outcomes when observed variability exceeds what a simple count model assumes. This primary endpoint is continuous age in months, not a count outcome; over-dispersion is not the relevant issue for interpreting the posted mean and standard deviation. More generally, statistical methods should match the outcome scale and distribution, but the model intended for this endpoint is not reported.

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("Treadmill Training Only", "Treadmill Training and Orthotic Use")
n   <- c(10, 7)
m   <- c(28.2, 28.3)
sp  <- c(8.3, 5.9)
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  Treadmill Training Only  10  28.200  8.300  22.263  34.137
CARM  Treadmill Training and Orthotic Use  7  28.300  5.900  22.843  33.757

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no posted secondary outcome measures. This limits the multiplicity questions that can be evaluated from the posted results, but it does not establish that no other outcomes were collected or examined. The registry record does not report a statistical analysis plan, a hierarchy of hypotheses, or a procedure for adjusting for multiple comparisons. It also does not report whether interim analyses were planned or conducted.

Multiplicity arises when several outcomes, time points, groups, or analyses are tested. In general, conducting many tests can increase the chance of at least one apparently notable result under a null hypothesis. Prespecifying a primary endpoint and analysis can help clarify which result is confirmatory, but the registry record does not provide enough detail to assess prespecification beyond identifying Pattern of Gross Motor Development as the primary outcome.

The listed primary outcome population is analysis on protocol. The record does not define protocol adherence or provide counts for randomized, treated, and analyzed participants by outcome. Overall enrollment is 22, while the endpoint summaries report 10 participants in the treadmill-training-only arm and 7 in the arm with orthotic use. The reason for the difference is not reported in the registry record.

No missing-data method, imputation procedure, sensitivity analysis, or explanation of unavailable endpoint measurements is reported. In general, missing outcomes can affect a group comparison if availability is related to participants' outcomes or group assignment. Without information about why data are missing and how they were handled, the potential influence cannot be assessed. No conclusion about the direction or size of any such influence is supported by the registry entry.

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 1% reporting threshold.

The registry reports serious adverse event figures separately from the primary outcome summaries. In the treadmill-training-only safety group, 10 participants were at risk, with 0 serious adverse events affecting participants and 0 deaths. In the treadmill-training-and-orthotic-use safety group, 12 participants were at risk, with 0 serious adverse events affecting participants and 0 deaths. The record also reports 0 other adverse events in each safety group.

These are counts within the recorded groups, not evidence that an event could not occur. The safety-group counts differ from the primary outcome counts: the outcome summaries include 10 participants in the treadmill-training-only arm and 7 in the orthotic-use arm, while the corresponding safety groups list 10 and 12 at risk. The registry record does not explain this difference, so the groups should not be assumed to represent identical analysis populations.

The absence of reported serious events describes the registry entry; it does not establish that all possible harms were assessed or ruled out. The registry record lists no top serious-event terms and gives no further detail on event definitions, collection procedures, duration of safety monitoring, or attribution. These figures should be read as the posted safety counts, not as a complete characterization of safety.

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

The record describes a randomized comparison of treadmill training alone with treadmill training combined with supramalleolar orthoses in infants with Down syndrome. For the primary outcome, age in months at walking development by the Gross Motor Function Measure, the posted mean is 28.2 months among 10 participants in the treadmill-training-only arm and 28.3 months among 7 participants in the combination arm. The corresponding standard deviations are 8.3 and 5.9 months.

These summaries describe the observed endpoint values in the two posted outcome groups. They do not include a formal group contrast or its uncertainty. Because the registry indicates that a two-arm comparison was not estimable, the mean values should not be treated as evidence that the groups were equivalent, nor should their closeness alone be taken as proof that adding orthoses had no effect. Equivalence requires an explicit margin and appropriate analysis, neither of which is reported.

The outcome addresses age at a defined walking-development milestone, not every component of gross motor development. Although upright play appears in the official title, no separate upright-play result is posted. The endpoint summaries also do not establish what happened for participants not included in the reported outcome counts. Their status and the reasons for the difference between enrollment and analyzed counts are not reported in the registry record.

The appropriate reading is therefore narrow: the registry contains descriptive mean and standard deviation summaries for the primary outcome, together with randomized design and safety-count information. It does not report the inferential analysis needed to quantify the contrast, its precision, or statistical compatibility with a null hypothesis. Nor does it provide enough information about missing data, adherence, or the analysis population to assess those issues fully. The results should not be extended beyond these posted data or interpreted as medical advice.

14. Why This Trial Matters Statistically

This trial raises a useful statistical distinction between a registered randomized design and the evidence that can be interpreted from posted outcome results. Randomization can support a fair group comparison when the analysis preserves the randomized assignment and the outcome data are sufficiently complete. Yet the primary outcome record contains arm summaries without an estimable two-arm comparison. Readers therefore have descriptive information but not a reported estimate of the randomized contrast or its uncertainty.

The endpoint also illustrates why outcome definition matters. Age in months at walking development is not a generic measure of every gross motor skill; it is an age tied to a specified assessment milestone. The monthly measurement window starts when a child can pull to stand and ends when the test determines the child is walking. A clear operational definition helps readers understand what the outcome represents, while the lack of an inferential comparison limits what can be learned about differences between arms.

Participant accounting is another important statistical issue. Enrollment is 22, but the primary outcome summaries have counts of 10 and 7. Without a participant flow or explanation, readers cannot determine how the analysis population relates to everyone enrolled or how unavailable outcomes were handled. The record's analysis-on-protocol description does not resolve this because the criteria are not reported.

Finally, the separate safety counts reinforce that populations can differ across outcomes: the orthotic-use safety group has 12 participants at risk, while its primary outcome summary includes 7. The discrepancy is not explained in the registry record. The trial is statistically informative as an example of why design labels, endpoint summaries, analysis populations, and uncertainty estimates must be read together, while avoiding conclusions that the posted comparison cannot support.

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.

Several limitations specific to this registry record constrain interpretation. First, the primary outcome is reported by arm as a mean and standard deviation, but a two-arm comparison is marked as not estimable. No group contrast, confidence interval, p-value, or model is reported. The statistical precision of any difference between the groups therefore cannot be assessed from the registry results.

Second, outcome counts are 10 for treadmill training only and 7 for treadmill training with orthotic use, compared with total enrollment of 22. The registry does not provide a participant flow, explain exclusions, or state why participants are absent from the outcome summaries. Although the primary population is called analysis on protocol, the record does not define this population or report an intention-to-treat analysis.

Third, the safety counts do not match the primary outcome counts in the orthotic-use group: 12 are listed at risk for safety, compared with 7 contributing to the primary outcome summary. The record does not explain how these groups were formed or whether the difference reflects different follow-up or analysis populations.

Fourth, the registry record does not report detailed eligibility criteria, baseline characteristics, the intervention schedule, adherence, the randomization procedure, allocation concealment, or masking beyond listing the study as unmasked. It does not report a statistical analysis plan, sample-size justification, interim analyses, missing-data methods, or sensitivity analyses. These omissions prevent assessment of several potential sources of bias and uncertainty.

Finally, only one primary outcome is posted and no secondary outcomes are posted. The absence of secondary results does not establish that no other outcomes were collected. The results therefore represent a limited record of the trial rather than a complete account of all outcomes or analyses.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Treadmill Training and Orthotic Use in Infants With Down Syndrome — NCT00825175.
• Registry record last updated 2017-12-04; status last verified 2017-10.
• Results first posted 2014-01-24.
• 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

NCT00825175 is a completed randomized, unmasked, parallel-group study sponsored by the University of Michigan. It enrolled 22 participants and compared treadmill training alone with treadmill training and supramalleolar orthoses in infants with Down syndrome. The registry lists the start as 2006-03 and primary completion as 2008-06.

The primary outcome was Pattern of Gross Motor Development: age in months at walking development as indicated by the Gross Motor Function Measure. The endpoint was assessed monthly from the ability to pull to stand until the test determined that the child was walking. The mean was 28.2 months with standard deviation 8.3 among 10 participants in the treadmill-only arm, and 28.3 months with standard deviation 5.9 among 7 participants in the orthotic-use arm.

A two-arm continuous comparison is not estimable in the registry record. No secondary outcome results are posted. Serious adverse events, other adverse events, and deaths are recorded as 0 in both safety groups; the at-risk counts are 10 and 12. The registry does not explain the difference between outcome and safety-group counts or provide a formal comparison analysis.