Local Injection of Pain Medication to Reduce Pain After Bone Marrow Procedures in Pediatric Neuroblastoma Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Local Injection of Pain Medication to Reduce Pain After Bone Marrow Procedures in Pediatric Neuroblastoma Patients (NCT02924324), a randomized na study. The primary outcome is Number of Participants Requiring Post-procedural Opioid Analgesia Per Study Arm.

2. Clinical Question

The clinical question concerns post-procedural opioid use as a recorded event, rather than a direct numerical measure of pain intensity. The study description also identifies pain reduction and opioid use as motivations for testing ropivacaine at the procedure site. Those aims do not establish what the observed outcome was: the number requiring post-procedural opioid analgesia is not reported in the registry record.

The crossover format makes treatment order relevant to interpretation. The registry lists one sequence in which propofol alone is used for the first bone marrow procedure and propofol with ropivacaine for the second, and another sequence with the order reversed. This permits a question about outcomes under the two procedural conditions, but a valid analysis needs to account for the paired nature of observations and any effects associated with order or procedure period. The statistical approach used to do so is not reported in the registry record.

3. Trial Design

This is a randomized, single-masked, crossover clinical trial. Its registered title describes a prospective study of procedural pain and recovery of quality of life in pediatric neuroblastoma patients undergoing bone marrow procedures. The registry lists enrollment as 56, phase as NA, and status as completed. The sponsor is Memorial Sloan Kettering Cancer Center. The listed study start is 2016-10, and primary completion is 2019-11.

The arm descriptions specify two sequences. In one, the first bone marrow procedure uses propofol, and the second uses propofol with ropivacaine. In the other, the first procedure uses propofol with ropivacaine, and the second uses propofol. Thus the sequence, rather than a permanently separate treatment group, distinguishes the registered arms. The record identifies the study model as crossover and allocation as randomized.

In a crossover design, participants receive the conditions in sequence, so observations under the conditions may be paired within participants. This can be useful statistically because a participant can serve as a reference for their own outcomes. It also means that order, period effects, or residual effects from an earlier procedure can matter to interpretation. These are general considerations for crossover studies; whether and how they were addressed in this trial is not reported in the registry record.

The masking entry is single, but the registry record does not identify who was masked or explain how masking was implemented. It also does not report the randomization procedure, allocation concealment, interval between procedures, eligibility criteria, or a statistical analysis plan. The record lists propofol, ropivacaine, a Wong-Baker FACES® Pain Rating Scale, and post-procedural quality of life among interventions. The listed primary outcome, however, is the number requiring post-procedural opioid analgesia.

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

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 Number of Participants Requiring Post-procedural Opioid Analgesia Per Study Arm, measured over within 24 hours (+/- 4 hours) post procedure.

The primary endpoint is the number of participants requiring post-procedural opioid analgesia per study arm. The specified timeframe is within 24 hours (+/- 4 hours) post procedure. This is a count of participants meeting an event definition, not a measure of the amount of opioid used, the timing of use within the window, or pain intensity itself.

An event-based endpoint can address whether participants required additional analgesia after the procedure. It may be clinically relevant to a study whose stated purpose includes evaluating pain and opioid use, but it captures only the defined event. A participant who required opioid analgesia and a participant who did not are distinguished by this outcome; differences in pain ratings, recovery, or the amount of medication are not conveyed by the count alone.

The registry record describes one outcome measure and gives the endpoint definition and timeframe, but does not report the number of participants meeting the endpoint in either sequence. It therefore does not provide a numerical estimate of the difference between the conditions or its precision. The record also does not report the outcome’s analysis population, handling of missing measurements, or a statistical comparison.

General statistical interpretation of a binary event count would ordinarily distinguish the observed count from the denominator at risk and would consider uncertainty around the comparison. For this endpoint, the registered design is crossover, so an analysis may also need to account for paired observations and procedure order. The registry record does not state how those features were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a crossover design imply?

In a crossover study, participants receive the study conditions in an assigned sequence rather than being observed under only one condition throughout. The registered sequences in this trial place propofol alone and propofol with ropivacaine at different bone marrow procedures, reversing their order between the sequences. In general, this design can support within-participant comparisons, because outcomes under the conditions can be related to the same participant. That potential advantage depends on having suitable observations from the relevant procedures and an analysis that recognizes their pairing.

Pairing matters because outcomes from the same participant are usually not treated as independent observations in the way outcomes from unrelated participants might be. A method that ignores this structure can misrepresent uncertainty. Crossover designs also call for consideration of procedure period and treatment order. A change between the first and second procedures could reflect the condition, a period effect, or both. A prior condition might also have residual effects on a later observation. These are general methodological considerations, not claims that such effects occurred in this trial. The registry record does not report the interval between procedures or the statistical methods used to handle pairing, order, period, or possible carryover.

What is the endpoint counting?

The registered primary endpoint counts participants requiring post-procedural opioid analgesia within 24 hours (+/- 4 hours) after the procedure. This is a binary event at the participant level: the participant either meets the stated requirement or does not. A group-level count summarizes how many participants experienced the defined event; it does not describe how severe pain was, how much medication was taken, or when within the stated window it was required.

For event data, interpretation ordinarily depends on both the event count and the relevant denominator. In a crossover setting, the unit of comparison and the handling of paired event status also need to be clear. For example, participants may or may not have the event under each condition, and the pattern across conditions can matter to a paired analysis. The registry record does not report outcome counts, denominators for the primary endpoint, or a method for comparing paired outcomes.

What can be inferred from a missing analysis?

The registry record lists no analysis entries and does not report an effect estimate, a confidence interval, or a hypothesis-test result for the primary endpoint. A general statistical analysis would ordinarily state the contrast being estimated, the population included, the treatment of incomplete observations, and the model or test used. In a randomized crossover trial, it would also explain how the sequence and repeated observations were represented. Those details are not reported in the registry record, so no particular model or test can be attributed to this study.

Confidence intervals are a general way to express uncertainty around an estimated effect: they describe a range of values compatible with the data under the model and assumptions used. Their precision depends on the information available and the analysis. Since no estimate or interval is reported for the primary endpoint, precision cannot be evaluated. A p-value would address compatibility with a specified null hypothesis under a statistical model; no p-value for the primary outcome is reported either. Neither the design nor the completed status supplies these missing results.

How should planning illustrations be interpreted?

Sample-size illustrations based on an observed effect are planning exercises, not observed power. The stated assumptions describe illustrations using a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and effects defined as fractions of an observed effect. Those are assumptions for the illustrations, not evidence of the trial’s own design rationale. The record does not report the trial’s sample-size justification or identify a planned effect size for design purposes. Any planning quantities should not be read as the number actually analyzed, a result, or proof that the study had a particular probability of detecting an effect.

For event outcomes, general planning calculations also depend on an event frequency and a specified comparison. The registry record does not report the primary endpoint event counts, so the observed event frequency and treatment contrast are not available from it. A planning illustration cannot fill that gap. The registry’s sample-size assumptions should be read only as planning context, not as a substitute for the trial’s outcome analysis.

What role do pain ratings and quality of life play?

The registry lists a Wong-Baker FACES® Pain Rating Scale and post-procedural quality of life among interventions, while the primary outcome is opioid analgesia requirement. The record does not give results for pain ratings or quality of life, nor does it provide further outcome definitions for them. Their inclusion in the intervention list does not establish that results were reported or indicate how these measures were analyzed. The primary endpoint should therefore be interpreted according to its stated event definition, without treating it as a direct pain rating or a quality-of-life measure.

10. Multiplicity, Missing Data and Analysis Populations

The registry record identifies the number of participants requiring post-procedural opioid analgesia as the primary outcome measure. It does not report a statistical analysis plan, analysis entries, hypothesis tests, or a strategy for controlling multiplicity. Although the record lists pain ratings and post-procedural quality of life among interventions, it does not supply corresponding result details or specify their status as secondary outcomes. Whether multiple outcomes or comparisons were formally tested, and how any multiplicity was handled, is not reported in the registry record.

Missing-data handling is also not described. The record does not report how many participants completed both procedures, whether any outcome observations were unavailable, how incomplete crossover pairs were treated, or whether any imputation was performed. These details matter because the interpretation of a within-participant comparison can depend on having outcome information under both conditions. Without the analysis population and missing-data approach, the available record cannot establish which participants contributed to an efficacy estimate.

The randomized sequences identify an order structure, but the analysis populations are not specified. The registry record does not say whether the primary analysis was based on all randomized participants, participants who completed both procedures, or another defined group. It also does not explain whether the analysis adjusted for order, period, or potential carryover. These absences limit assessment of the methods and prevent reconstruction of a primary result from the registry information.

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.

The registry lists zero serious adverse events affected and zero other adverse events affected in each of the Propofol and Propofol and Ropivacaine groups. Each group entry lists 56 at risk. Separately, the death entry is 12 for each group. These are the safety figures recorded in the registry; they are not results for the primary opioid-analgesia endpoint.

The record does not explain the timing, attribution, or relationship to treatment of the listed deaths. It also does not describe how adverse events were collected, the duration of safety follow-up, or whether the group entries refer to the same participants observed across crossover periods. In a crossover study, group labels describing treatment sequences should not automatically be interpreted as independent permanent cohorts. The registry does not provide enough detail to resolve how the safety summaries relate to exposure periods.

Zero affected events in a registry entry should be read as the recorded count, not as proof that the underlying risk was absent. The record offers no event-level descriptions or uncertainty estimates for these figures. The death counts should not be interpreted as treatment-caused deaths: causality and context are not reported. Taken together, the safety entries are limited summaries whose meaning cannot be fully assessed from the registry record alone.

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

The registry record documents a randomized, single-masked crossover comparison of propofol alone with propofol plus ropivacaine during bone marrow procedures in pediatric neuroblastoma patients. It specifies the primary endpoint as the number requiring opioid analgesia within 24 hours (+/- 4 hours) after the procedure. That information clarifies the intended question and the event being counted.

It does not establish the observed result. The endpoint counts for the sequences are not reported in the registry record, and there is no reported effect estimate, confidence interval, or statistical test for the primary outcome. The record therefore does not support a claim that one condition had more or fewer participants requiring opioid analgesia, nor does it permit assessment of the magnitude or precision of a difference.

The endpoint is not interchangeable with pain intensity, opioid dose, recovery, or quality of life. The record mentions a pain-rating scale and post-procedural quality of life, but does not report their results. Nor does the primary endpoint alone describe the full experience of pain after a procedure. It captures whether opioid analgesia was required according to the defined outcome, within the specified timeframe.

The registry status is completed, but that designation is not a result. Likewise, the enrollment entry does not establish how many participants contributed usable observations to a primary analysis. The crossover design calls for attention to paired outcomes and order, but the analysis details are not reported. The most defensible interpretation is therefore that the registry record defines a clinically focused comparison while leaving its outcome findings and statistical uncertainty unreported.

13. Why This Trial Matters Statistically

This trial raises a useful statistical design question: how should a treatment comparison be evaluated when the same participant undergoes procedures under both conditions? A crossover design can make within-participant information available, which may help separate individual-level variation from differences associated with the procedural conditions. At the same time, the sequence and timing of procedures become important. An analysis needs to represent the paired observations and consider whether order or period could influence results. The registry identifies the design and sequences, but does not report how these issues were handled.

The endpoint also illustrates why outcome definition matters. Counting participants who require opioid analgesia is not the same as measuring pain intensity or the quantity of medication used. A clear event definition and timeframe support consistent interpretation, while leaving other dimensions of recovery outside that endpoint. The record states a specific post-procedure window but does not report the observed counts or other outcome details.

Finally, the trial illustrates the distinction between a registered question and a reported result. A completed study with a defined primary endpoint can still lack the information needed to estimate an effect or judge its precision in the registry record. The design, enrollment, and safety entries do not substitute for outcome estimates and an account of the analysis. For statistical readers, identifying both what the record specifies and what it omits is essential to keeping design description separate from evidence about outcomes.

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 registry record does not report the primary endpoint counts, denominators, or comparative analysis. This is the central limitation for interpreting the trial statistically: neither the direction nor size of the endpoint contrast can be established from the record, and its precision cannot be judged.

Important design and analysis details are also absent. The record does not give eligibility criteria, the method of randomization, who was masked, the timing between procedures, completion by sequence, or the number included in an analysis. It does not state how paired outcomes, order, period, or possible carryover were handled. Missing-data methods and the analysis population are not reported.

The primary outcome is an event count for opioid analgesia requirement, not a direct measurement of pain severity, medication amount, or quality of life. Although the record lists a pain scale and post-procedural quality of life, it gives no results for these measures. It also does not report outcome definitions for them beyond their listing.

The safety entries lack context about follow-up, event ascertainment, attribution, and the relationship of deaths to treatment or procedures. The registry’s completed status and enrollment entry cannot resolve these gaps. Accordingly, the record supports description of the planned comparison and endpoint, but not a complete assessment of efficacy, safety, or statistical robustness.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Local Injection of Pain Medication to Reduce Pain After Bone Marrow Procedures in Pediatric Neuroblastoma Patients — NCT02924324.
• Registry record last updated 2022-11-08; status last verified 2021-10.
• Results first posted 2022-04-26.
• 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 RePPAIR, a randomized, single-masked crossover trial in pediatric neuroblastoma patients undergoing bone marrow procedures. The registered sequences compare propofol alone with propofol plus ropivacaine, with treatment order reversed between sequences. Enrollment is listed as 56; the record lists phase as NA, status as completed, start as 2016-10, and primary completion as 2019-11.

The primary outcome is the number requiring post-procedural opioid analgesia within 24 hours (+/- 4 hours). Outcome counts and a statistical comparison are not reported in the registry record. The record also lists adverse-event counts, but provides limited context for interpreting the death entries or safety follow-up. Analysis populations, missing-data handling, and methods for the crossover structure are not reported.