A Randomized Controlled Trial of Three Non-pharmacologic Analgesic Techniques for Casting of Clubfoot Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Randomized Controlled Trial of Three Non-pharmacologic Analgesic Techniques for Casting of Clubfoot Infants (NCT02395185), a randomized na study. The primary outcome is NIPS (Neonatal Infant Pain Scale).

2. Clinical Question

3. Trial Design

This was a randomized, double-masked, crossover trial of three non-pharmacologic approaches during casting for clubfoot in infants. The registry record gives an enrollment of 33 and identifies the study as completed. Its recorded start is 2013-01, and its primary completion is 2014-10. Shriners Hospitals for Children is listed as the sponsor.

The three conditions were sucrose bottle administration, milk bottle administration, and water bottle administration. A crossover design involves assessing conditions within participants rather than assigning each participant to only one condition; generally, this can make within-person comparisons useful because each participant can serve as their own reference. The record specifically notes that multiple casts were assessed for each participant. However, it does not describe the order of conditions, the number of casts per participant, any interval between casts, or how condition sequences were assigned.

Double masking is the registry’s design designation. For NIPS scoring, it specifically says trained study personnel were blinded to the contents of the bottle. The record does not explain who else was masked or how masking was maintained. Randomization and masking can help limit bias, but the designation alone does not establish that all sources of bias were controlled.

The primary measure was the mean NIPS score, with standard deviation as its dispersion measure. Heart rate and oxygen saturation were listed as secondary outcomes. The registry record does not report a statistical analysis plan, a sample-size justification, or the results for these outcomes.

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: Because this was a crossover design, multiple casts were assessed for each participant

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: Analysis included 43 casts receiving sucrose, 37 casts receiving milk or formula, and 42 casts receiving water

6. Primary Endpoint

The registry lists the primary outcome as NIPS (Neonatal Infant Pain Scale), measured over Scoring will be recorded at minute intervals starting at 2 minutes prior to casting and ending at 3 minutes post casting..

The primary endpoint was the Neonatal Infant Pain Scale (NIPS), a behavioral measure used to characterize pain responses in infants. The scale brings together observations across facial expression, cry, breathing patterns, arms, legs, and state of arousal. The registry describes scores from 0 to 7, with 0 indicating no pain and scores greater than 4 categorized as severe pain.

Each cast visit was to be videotaped before, during, and after casting, then reviewed for subjective NIPS scoring. A trained study staff member blinded to the bottle contents was to score the recordings at minute intervals. The stated timeframe begins 2 minutes before casting and ends 3 minutes after casting. The planned pre-casting score was the average of the first 3 minute scores before casting; the during-casting score was the average of scores recorded at 1-minute intervals during casting; and the post-casting score was the average of the 3-minute scores after casting.

Using a behavioral scale allows the study to assess observable responses during a procedure. The endpoint description does not establish how closely those responses correspond to an infant’s subjective experience. The registry record does not report actual NIPS scores, variability estimates, or comparisons among bottle conditions.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe? The primary outcome is characterized as a mean of a continuous measure, with standard deviation. A mean describes the central level of scores in a group of observations. A standard deviation describes how spread out those scores are around the mean. These summaries can help readers understand the score distribution, but they do not by themselves show the uncertainty in a comparison between conditions. The registry record does not report the means or standard deviations for the NIPS outcome.

Why does the crossover design matter? General statistical context: In a crossover study, participants may be observed under more than one condition. Comparing a participant’s responses across conditions can account for stable individual characteristics, but the observations are not necessarily independent. The analysis may need to account for within-participant correlation and for the structure of repeated observations. The registry record states that multiple casts were assessed per participant, but does not report the condition sequence, number of observations per participant, or the method used to handle repeated scores. It also does not report whether there were period or order effects or how such effects were considered.

Why is the timing of scores important? NIPS scoring was planned before, during, and after casting, with time-based recordings and averages for those periods. These are distinct windows around the procedure, and a result for one window would not necessarily describe another. The record does not report the numerical scores, the number of observations contributing to each average, or a primary comparison tied to a particular scoring window. A single overall treatment effect should therefore not be inferred from the endpoint description.

What does a confidence interval add? General statistical context: A confidence interval expresses the uncertainty around an estimated effect under the assumptions of the analysis. It can indicate which effect sizes are compatible with the data and analysis, rather than only whether a significance threshold was crossed. The registry record does not report confidence intervals or effect estimates for the primary outcome, so the precision of any difference between conditions cannot be assessed.

Why can repeated measurements require a specialized model? General statistical context: When observations are clustered within a person, scores from that person may be more alike than scores from different people. Ignoring that dependence can make uncertainty estimates unreliable. Methods for repeated or clustered data can represent the relationship among observations, but the appropriate method depends on the design and analysis question. No statistical model or variance method is reported in the registry record. The information available is therefore insufficient to assess whether the reported analysis, if any, accounted for participant-level clustering.

What does the sample-size planning description mean? The registry record describes a planning illustration based on the observed effect. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is defined as a stated fraction of the observed effect. The record does not provide numerical planning estimates or the numerical observed effect. These are planning assumptions, not evidence that the study had a particular probability of detecting an effect. Sample-size illustrations should not be described as observed power.

What can be concluded from the analysis information? The registry record does not report an analysis plan, effect estimates, tests, or confidence intervals. It also does not report whether analyses were adjusted, which analysis population was used, or how the different scoring periods were handled. The absence of those details prevents readers from evaluating the statistical approach or reconstructing the comparisons. It also means that no result should be inferred from the endpoint definitions or study design alone.

10. Multiplicity, Missing Data and Analysis Populations

The study includes a primary NIPS outcome assessed around casting and two listed secondary outcomes: heart rate and oxygen saturation. The NIPS description distinguishes pre-casting, during-casting, and post-casting scores. Considering several outcomes, time periods, or condition comparisons can create a multiplicity issue: general statistical context, the more comparisons examined, the greater the chance that an apparently notable result arises by chance if no adjustment or other prespecified strategy is used. The registry record does not report how multiplicity was addressed, whether one time period was designated as the primary comparison, or which comparisons were planned.

The registry record lists zero analyses. It does not provide an analysis plan or results for the primary or secondary outcomes, nor does it state which analysis population was used. Therefore, the handling of participants or casts without usable measurements, exclusions, or deviations from the planned scoring schedule is not reported in the registry record.

Missing-data methods are also not reported in the registry record. It does not describe whether missing observations occurred, how they were handled, or whether any sensitivity analyses were performed. In a crossover study with repeated casts, the availability of observations may vary across conditions or scoring periods; general statistical context, such variation can affect which comparisons are supported and how representative the analyzed observations are. The record does not provide information to assess whether this issue arose in this trial.

These omissions do not establish that multiplicity or missingness caused bias. They mean that the statistical handling and its implications cannot be evaluated from the registry record.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event record lists zero serious adverse events among the stated at-risk counts for sucrose, milk or formula, and water. It lists one other adverse event for sucrose and zero other adverse events for milk or formula and water. These are the registry’s reported counts for the named groups; the record does not describe the nature of the other event or attribute it to a study condition.

The listed at-risk counts are 29 for sucrose, 26 for milk or formula, and 26 for water. These are group-specific registry counts and should not be added together to infer the number of distinct participants, particularly because the trial used a crossover design and multiple casts were assessed per participant. The adverse-event figures alone do not establish comparative risk or explain how events were collected or adjudicated.

The deaths fields are not populated, so deaths are not reported in the registry record. No serious adverse-event terms are listed. The counts describe what the registry record reports; they should not be treated as proof that no unreported events occurred or as a measure of the primary pain outcome.

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

This trial was designed to compare three bottle-administered, non-pharmacologic conditions during casting for clubfoot in infants, using NIPS as its primary outcome. The record describes randomization, double masking, and a crossover model, along with an endpoint intended to capture behavior before, during, and after casting. These details clarify the clinical question and the planned measurement approach.

The registry record does not report NIPS results or statistical comparisons. It therefore does not show which condition had higher or lower scores, whether any observed differences were compatible with chance, or how precisely an effect was estimated. The result cannot be interpreted as evidence that one condition was better or worse than another. No treatment effect should be inferred from the design description, planned outcome, or safety counts.

The posted adverse-event counts report zero serious adverse events in the listed groups, and one other event in the sucrose group. Those counts provide limited descriptive safety information, but the event description, follow-up details, and deaths are not reported in the registry record. They do not establish a comparative safety profile.

More generally, a trial design can make a comparison possible, but the design does not substitute for the observed data and analysis. Without outcome summaries, effect estimates, uncertainty measures, and an account of the repeated-measures analysis, readers cannot judge the magnitude or precision of differences among conditions. The registry record also does not provide enough information to evaluate missing observations, multiplicity, or the analysis population.

The defensible interpretation is therefore limited to what the record documents: a completed randomized crossover study with a defined behavioral pain measure and reported adverse-event counts. Whether NIPS scores differed across sucrose, milk or formula, and water is not reported in the registry record.

13. Why This Trial Matters Statistically

This trial raises a statistical question in a setting where measurement is based on observable behavior during a procedure. NIPS combines several behavioral categories into a score, and the registry describes recording that score before, during, and after casting. The choice of outcome, timing, and scoring process matters because an analysis needs to match the way data were collected and the clinical question being asked.

The crossover structure also makes the analysis important. Repeated casts and multiple conditions within participants can produce related measurements. General statistical context: accounting for that dependence is important when estimating uncertainty and comparing conditions. The record establishes that multiple casts were assessed per participant but does not report the analytical method used to address repeated observations.

Masking is relevant to a behavioral endpoint because scoring involves subjective evaluation. The registry states that trained study personnel scoring the videos were blinded to bottle contents. This is a useful design detail, while the absence of results and fuller analysis information limits assessment of how the study findings should be interpreted.

The registry record’s main statistical lesson is the distinction between a trial’s design and its evidence about an effect. A randomized, masked crossover design may support informative comparisons when analyzed and reported appropriately, but the record does not give the outcome estimates needed to judge those comparisons. Reporting the period-specific scores, the handling of repeated casts, and the uncertainty around treatment contrasts would be necessary to evaluate the primary question. Those results and methods are not reported in the registry record.

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 central limitation for interpretation is that the registry record does not report the primary NIPS results. It gives no outcome means, standard deviations, effect estimates, confidence intervals, or p-values. It also does not report results for heart rate or oxygen saturation. Consequently, neither the direction nor the precision of any comparison can be assessed.

Several design details that matter for a crossover analysis are not reported in the registry record, including condition order, the number of casts assessed per participant, and the interval or other circumstances between casts. The record does not describe whether order or period effects were assessed, or how repeated observations within participants were modeled. These are reporting gaps, not evidence that a particular problem occurred.

The registry does not report participant flow, the analysis population, missing observations, or methods for handling missing data. It also does not give a statistical analysis plan or explain how multiple conditions, time periods, and secondary outcomes were handled. Without these details, readers cannot assess the extent of prespecification or the robustness of the planned comparisons.

The endpoint relies on video review and subjective scoring, although the record says scoring personnel were trained and blinded to bottle contents. Further details about scorer agreement or quality control are not reported. Finally, adverse-event information is limited to counts; event descriptions and deaths are not reported in the registry record. These limitations restrict interpretation of both efficacy-related outcomes and safety, without implying that the study necessarily had flawed conduct.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Randomized Controlled Trial of Three Non-pharmacologic Analgesic Techniques for Casting of Clubfoot Infants — NCT02395185.
• Registry record last updated 2017-12-15; status last verified 2017-05.
• Results first posted 2017-12-15.
• 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 completed, randomized, double-masked crossover trial of sucrose, milk or formula, and water bottle administration during casting for clubfoot in infants. Enrollment is listed as 33. The primary outcome was mean NIPS score, with standard deviation, assessed before, during, and after casting; heart rate and oxygen saturation were listed as secondary outcomes.

The record reports zero serious adverse events in each named group and one other adverse event in the sucrose group, with none listed for the other groups. It does not report the primary outcome results, secondary outcome results, statistical comparisons, or a statistical analysis plan. Thus, the relative NIPS scores and the precision of any differences are not reported in the registry record.