The Effects of Ankle Foot Orthoses on Gait Efficiency in Children With Acute Lymphoblastic Leukemia and Foot Drop: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effects of Ankle Foot Orthoses on Gait Efficiency in Children With Acute Lymphoblastic Leukemia and Foot Drop (NCT01001390), a randomized na study. The primary outcome is Net Oxygen Consumption During the Six Minute Walk Test Among Study Participants Under the Two Walking Conditions, With and Without AFO..

2. Clinical Question

The study asks whether oxygen use during walking differs between the two conditions for children with foot drop associated with acute lymphoblastic leukemia. The registry summary describes measuring oxygen use during each walk and comparing the walk with the brace to the walk without it. The primary outcome is net oxygen consumption: walking oxygen consumption minus sitting oxygen consumption, adjusted by the total mass carried during the walk.

The planned comparison is within a crossover design: participants were to walk in both conditions, with the order assigned to a group. This design can support a comparison that accounts for differences between participants, because each participant can contribute observations under both conditions. That advantage depends on collecting usable measurements in both conditions. The registry record says no data were collected for analysis, because neither participant agreed to wear an AFO. Consequently, the clinical question remains unanswered by the posted outcome results; the record does not provide an estimated difference in oxygen consumption or its precision.

3. Trial Design

The registry describes a randomized, unmasked crossover study of an AFO device. The condition list includes foot drop and acute lymphoblastic leukemia. The study status is terminated, and the registry reports enrollment of two participants. The listed phase is not applicable. The sponsor is St. Jude Children's Research Hospital. The recorded start is 2009-10 and primary completion is 2011-06.

Participants were assigned to one of two sequences. Group One was to complete a six-minute walk test with the AFO, rest for fifteen minutes, then complete another six-minute walk without the AFO at a similar speed. Group Two was to walk without the AFO first, rest for fifteen minutes, then walk with it at a similar speed. Thus, the order of the conditions differed between the groups. The registry lists no masking.

In a crossover study, the same participant is intended to receive or experience each comparison condition. Randomizing the order can help avoid always placing one condition first, while the rest period is part of the stated walk sequence. These design features describe the plan; the registry does not report whether order effects or other sequence-related effects were assessed. Nor does it report a statistical analysis plan or explain the decision to terminate the study.

Crucially, the posted primary outcome population states that no data were collected for analysis: neither enrolled participant agreed to wear an AFO. The randomized sequence therefore did not yield the paired outcome observations needed to estimate the planned with-versus-without comparison. The record does not report whether either participant completed a walk without the device, so completion of that condition should not be inferred from the enrollment or safety listings.

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: Participants had a diagnosis of acute lymphoblastic leukemia and had developed foot drop during treatment for their leukemia. Randomization was to one of two reporting groups: (1) With then without AFO, and (2) Without then with AFO.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: No data was collected for analysis. Two participants were enrolled, however, neither participant agreed to wear an ankle foot orthoses.

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: Two participants were enrolled, however, neither participant continued to wear their ankle foot orthoses after the initial visit.

6. Primary Endpoint

The registry lists the primary outcome as Net Oxygen Consumption During the Six Minute Walk Test Among Study Participants Under the Two Walking Conditions, With and Without AFO., measured over Baseline.

The primary endpoint is net oxygen consumption during the six-minute walk test under the two walking conditions, with and without an AFO. The registry defines net oxygen consumption as walking oxygen consumption minus sitting oxygen consumption, then adjusted by total mass in kilograms. The mass adjustment includes body mass, socks, appropriate shoes, helmet, mouth piece system, and, for walks with the AFO, the mass of the brace.

Subtracting sitting oxygen consumption is intended to distinguish oxygen use associated with walking from oxygen use at rest. Adjusting by total carried mass expresses the measure in relation to the load included in the test, including the brace in the AFO condition. These are features of the endpoint definition, not evidence that the endpoint was measured or that the adjustment produced a particular result.

Oxygen consumption is used in this study as a measure of the energetic demand of walking. Comparing the measure across the two conditions addresses the study's stated question about gait efficiency. The record gives no unit, parameter type, or measure of dispersion for the primary endpoint, and it reports no outcome values. It also states that no data were collected for analysis because neither participant agreed to wear an AFO. Therefore, the endpoint's definition can be described, but its observed level and the difference between conditions are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design compare?

In a crossover design, a participant is intended to receive or experience each condition, and the outcome under one condition is compared with the outcome under the other. A within-participant comparison can account for characteristics that remain relatively stable within a participant, because those characteristics are shared across that participant's measurements. This is a general statistical feature of crossover designs, not a finding from this study.

Here, the registry describes two sequences: AFO then no AFO, and no AFO then AFO. Random allocation assigns the order rather than making every participant follow the same order. Order can matter if experience in the first condition affects performance in the later condition. Resting between walks is part of the recorded procedure, but the registry does not report a test for order effects, a carryover assessment, or a statistical method for handling sequence. The design plan therefore should not be mistaken for proof that these issues were assessed.

What would the primary comparison require?

The primary outcome is a paired comparison of net oxygen consumption under the two walking conditions. To estimate such a contrast, usable outcome measurements would be needed for both conditions for participants included in the analysis. As a general statistical point, a paired estimate describes the average within-participant change, while its uncertainty depends on the variability of those paired changes. The registry reports no outcome measurements, estimate, or dispersion. Its stated reason is that neither participant agreed to wear an AFO, so the intended comparison could not be analyzed.

What does randomization contribute?

Randomization of condition order can reduce systematic assignment of one sequence to particular participants. In a small study, however, randomization does not ensure that the sequences are balanced on participant characteristics, nor does it supply outcome observations that were not collected. Here, the registry's enrollment and outcome statements do not support an estimate of a sequence effect or a randomized treatment contrast. The record does not report a statistical plan explaining how randomization would have been incorporated into analysis.

How should precision be understood?

Generally, a confidence interval describes a range of values compatible with the data and a chosen statistical procedure. It communicates uncertainty around an estimated effect; it is not a guarantee that the true effect lies within the interval. No confidence interval is reported for this primary outcome, because the record reports no data collected for analysis. Thus, there is no precision estimate to interpret. A missing interval cannot be read as a narrow interval, a broad interval, or evidence of equivalence.

Dispersion measures, such as a standard deviation, describe variability in observations. The primary outcome record gives no dispersion measure, and no unit or parameter type is listed. Without outcome observations and variability information, the magnitude and precision of an estimated contrast cannot be evaluated from the registry record.

What is the role of a p-value?

In general, a p-value is calculated under a specified statistical model and null hypothesis. It is not the probability that the null hypothesis is true, and it does not show whether an estimated effect is important. No p-value or inferential test is reported for the primary outcome. The record also does not report a prespecified analysis method, so a particular test should not be attributed to the investigators.

Why does over-dispersion matter?

As a general statistical concept, over-dispersion occurs when count outcomes vary more than a model assumes. If that extra variability is ignored, uncertainty can be understated and statistical tests can be poorly calibrated. This concept is relevant in general when analyzing variable event counts, but the registry does not report an analysis of the secondary outcome, which is a count of participants with improvement in gait efficiency. No distributional model or dispersion assessment is reported, and no such method should be inferred.

How should planning calculations be read?

The registry's stated sample-size assumptions describe a planning illustration based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The assumed target effect is a stated fraction of the observed effect. These are planning assumptions, not a description of the trial's own design rationale. Because no primary outcome data were collected for analysis, the record provides no observed effect estimate to anchor such an illustration. Any sample-size value derived from planning assumptions would be a planning illustration, not observed power. The registry does not report the trial's own sample-size justification.

The record lists no analyses and gives a skip reason of fewer than two arms in the primary outcome. These entries are consistent with the absence of an analyzable primary comparison but do not disclose a model, estimator, adjustment procedure, or inferential testing strategy. The statistical analysis plan is not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and a secondary outcome. The primary outcome concerns net oxygen consumption during the six-minute walk test with and without an AFO. The secondary outcome is the number of participants with improvement in gait efficiency while using an AFO. The record does not report how the investigators planned to control multiplicity across outcomes or any additional statistical tests. It does not describe a hierarchy for testing outcomes or identify which analyses, if any, were considered confirmatory.

No analyses are listed, and no primary outcome data were collected for analysis. The registry states that neither participant agreed to wear an AFO. This is not a case in which an estimated result is reported with some outcome values missing; rather, the record says the outcome was not collected for analysis. The reason for the lack of primary outcome data is reported, but the registry does not describe a missing-data strategy, imputation, sensitivity analysis, or an assessment of how missingness might affect an estimate.

The record does not identify an analysis population, such as all randomized participants or participants with complete paired measurements. It also does not describe exclusions, adherence-based analyses, or how any incomplete walk data would have been handled. These details are not reported in the registry record. In general, an analysis population defines which participants' data enter an estimate; that choice can affect interpretation, particularly when the intended outcome requires observations under both conditions. Here, the absence of a reported estimate means that no analysis population can be evaluated from the posted results.

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 5% reporting threshold.

The registry lists serious adverse events and other adverse events by group. For Group 1: With Then Without AFO, the record lists two participants at risk, zero serious events, and zero other events. For Group 2: Without Then With AFO, it lists zero participants at risk, zero serious events, and zero other events. The group listings therefore have different denominators: Group 2 has no participants at risk in the posted safety record.

These entries should not be read as a comparison of event rates between the sequences. The group with zero participants at risk contributes no exposed participants for interpreting its event counts. In general, a zero event count among a small number of people does not establish that an event cannot occur or precisely characterize risk. The registry does not report exposure time or further details about adverse-event monitoring.

Deaths are recorded as null for both groups, which means death counts are not reported in the registry record. No serious adverse-event terms are listed. The safety figures are separate from the primary endpoint, and they do not provide evidence about net oxygen consumption or gait efficiency.

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

The record establishes that a randomized, unmasked crossover study was planned to compare net oxygen consumption during walking with and without an AFO in children with acute lymphoblastic leukemia and foot drop. It documents the two intended condition orders and the endpoint's calculation. It also reports that two participants enrolled and that neither agreed to wear an AFO, leaving no primary outcome data for analysis.

What the record does not establish is whether wearing an AFO changes oxygen consumption, whether any change is large or small, or how precisely a difference could be estimated. No primary outcome values, effect estimate, confidence interval, or p-value are reported. The lack of an estimate is not evidence of no effect, equivalence, or a particular direction of effect. It reflects that the planned primary comparison was not available for analysis.

The posted secondary outcome does not resolve this limitation: the registry lists the outcome definition but no results. The adverse-event entries likewise do not answer the clinical question. They describe the recorded safety counts by group, with no participants at risk listed for Group 2, and do not support a general conclusion about safety.

The trial's termination status is reported, but the reason for termination is not reported in the registry record. The record also does not explain why participants declined the AFO, whether alternative measurement procedures were considered, or whether additional study activity occurred. Those details should not be inferred. The appropriate interpretation is limited to the record: a comparison was planned, but no analyzable primary outcome result was posted.

13. Why This Trial Matters Statistically

This study illustrates the distinction between a planned statistical comparison and an estimable treatment contrast. A crossover design can be useful when each participant can provide outcome measurements under both conditions. The within-participant structure may reduce the influence of stable differences between participants. But the design's statistical advantage depends on collecting the measurements required for the comparison. The registry reports that neither participant agreed to wear an AFO and that no primary outcome data were collected for analysis.

The record also shows why enrollment alone is not a sufficient guide to the information available for an endpoint. The enrollment count is reported, but enrollment does not establish that participants contributed usable observations under each condition. Without those measurements, the planned comparison has no observed effect estimate and no precision measure. A registry can therefore document a trial's question and procedure while offering no statistical answer to that question.

For statistical interpretation, it is important to distinguish a null result from an unavailable result. A null result would require an analysis that estimates an effect and uncertainty; this record reports no such analysis. Treating the absence of an estimate as a finding of no difference would misrepresent the evidence.

The case further emphasizes that group-level safety counts depend on who was at risk. One sequence lists zero participants at risk, so its zero event counts cannot be treated as equivalent to zero events among exposed participants. Clear denominators are necessary for readers to understand what a count does and does not represent.

Finally, a stated planning framework is not a substitute for trial-specific evidence. Planning illustrations based on an observed effect require an effect estimate, while this record reports no analyzable primary outcome. The registry does not report the trial's own sample-size justification or statistical plan. Keeping those distinctions clear prevents planned methods, unavailable results, and observed findings from being conflated.

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 principal limitation for statistical interpretation is that no primary outcome data were collected for analysis. The registry attributes this to neither participant agreeing to wear an AFO. Without the AFO condition measurements needed for the intended comparison, the study record cannot provide an estimate of net oxygen consumption under the two conditions. No confidence interval, dispersion measure, test statistic, or p-value is reported.

The reported enrollment is two, and the study status is terminated. The registry does not report the reason for termination or explain whether any protocol changes were made. It also does not state whether participants completed the walks without an AFO, so completion of a comparison condition cannot be assumed. The record does not report adherence, withdrawals, or participant-level outcome data.

The registry lists the design as randomized and crossover, but does not report the randomization procedure, the allocation sequence, or the planned handling of sequence and period effects. Masking is listed as none. The statistical plan, analysis population, missing-data method, and multiplicity approach are not reported in the registry record. The record also gives no unit, parameter type, or measure of dispersion for the primary endpoint.

The safety listing has zero participants at risk in Group 2, limiting interpretation of that group's event counts. Deaths are not reported, and there are no serious adverse-event terms listed. These record-level details do not allow broader safety conclusions. Taken together, the limitations prevent estimation of either the primary effect or its uncertainty and constrain interpretation to the study plan and the absence of analyzable results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Effects of Ankle Foot Orthoses on Gait Efficiency in Children With Acute Lymphoblastic Leukemia and Foot Drop — NCT01001390.
• Registry record last updated 2014-03-27; status last verified 2014-01.
• Results first posted 2014-02-28.
• 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 randomized, unmasked crossover study of an AFO for children with acute lymphoblastic leukemia and foot drop. Its primary outcome is net oxygen consumption during the six-minute walk test with and without the device. The two planned sequences placed the AFO condition either before or after the condition without the device, with a fifteen-minute rest between walks.

The record reports enrollment of two participants and a terminated study. It states that no primary outcome data were collected for analysis because neither participant agreed to wear an AFO. No primary or secondary outcome analysis is reported, and the registry gives no effect estimate or measure of precision. The reason for termination, statistical analysis plan, sample-size justification, and missing-data procedures are not reported in the registry record.