Managing Pain and Symptom Burden Caused by Chemotherapy in People With Myeloma or Lymphoma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Managing Pain and Symptom Burden Caused by Chemotherapy in People With Myeloma or Lymphoma (NCT04459416), a randomized phase 3 study. The primary outcome is the Number of Patients Using Opioids at a Given Time.

2. Clinical Question

OPTIMAL-HiChemo asks whether adding acupuncture to usual pain management changes opioid use among people with multiple myeloma, Hodgkin disease, or non-Hodgkin lymphoma undergoing high-dose chemotherapy. The comparison is acupuncture plus usual care versus usual care alone. Usual care includes opioid medication when needed for severe pain; participants in the acupuncture group could also receive opioids as backup pain relief if acupuncture did not prevent severe pain.

The primary question is framed around opioid use at day 7. The registry describes counting patients using opioids at that time, with medication records and a urine drug test used for assessment. Researchers also aim to learn about other symptoms caused by cancer treatment and quality of life. The registry lists five outcome measures, but it does not provide a single numerical comparison for the primary outcome.

The question is therefore about the effect of assigning an acupuncture-plus-usual-care strategy, compared with usual care, on opioid use and related outcomes. It is not a comparison of acupuncture with no pain management: both groups receive usual care, and opioid medication remains available in both. Because the trial is unmasked, participants and care teams know which strategy is assigned. That context matters when interpreting reported outcomes and how they were assessed.

The registry record lists an enrollment of 299 and identifies the study as randomized and phase 3. Its status is active, not recruiting. No primary outcome estimate, uncertainty interval, or inferential test is reported in the registry record, so the available description establishes the question and measurement approach, but not the size or precision of a comparative effect.

3. Trial Design

The registry describes a randomized, parallel-group, phase 3 trial with no masking. Participants were assigned to usual care plus acupuncture or usual care alone. The enrollment listed is 299. The conditions listed are multiple myeloma, Hodgkin disease, and non-Hodgkin lymphoma. Memorial Sloan Kettering Cancer Center is named as the sponsor.

In the acupuncture arm, treatment was planned to start on Day 0 and continue once daily through Day 15 while the participant was an inpatient or attended clinic for post-transplantation follow-up. The description says acupuncture was intended to prevent severe pain, with opioid medication available as backup if severe pain was not prevented. The usual-care arm received the routine pain-management approach, including opioid medication when needed for severe pain.

The record lists a study start date of 2020-06-30 and a primary completion date of 2024-07-02. Its current status is active, not recruiting. These dates and status describe the trial record; they do not establish that all follow-up or analysis is complete.

Important operational details are not reported in the registry record. These include how the randomization sequence was generated, whether allocation was concealed before assignment, the exact usual-care procedures, and the protocol for deviations from assigned care. The registry also does not describe masking of outcome assessors. Since the trial is recorded as unmasked, interpretation should account for the possibility that knowledge of assignment could affect care, participant reporting, or outcome assessment. The absence of those details does not show that a procedure was or was not used; it means the registry record does not specify it.

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

Reasons for not completing this period:

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 the Number of Patients Using Opioids at a Given Time, measured over at day 7.

The primary endpoint concerns the number of participants using opioids at day 7. The registry says opioid use is assessed by review of medication records and a urine drug test. It also describes the number using opioids at a given time in relation to the total number randomized to that group at Day 7. The endpoint is therefore intended to capture opioid use at a specified point during care rather than a measure of pain intensity alone.

Opioid use is relevant to the trial question because the intervention is described as an opioid-sparing pain-treatment strategy. A count of participants using opioids can show how many people in each assigned group had opioid use recorded at the specified time. Medication records and urine testing provide different sources of information about use, although the registry record does not give further details about how results from these sources were combined or adjudicated.

In general, a point-in-time endpoint can be straightforward to interpret, but it does not describe the full course of pain or medication use. It does not, by itself, summarize opioid dose, duration, pain relief, or later use. The primary outcome has several categories or time points in the registry, and no single primary comparison is reported. The registry record therefore does not provide the group counts or an estimated between-group effect for the day-7 endpoint.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation depends first on distinguishing a trial design from a trial result. Randomization describes how assignment is intended to create comparable groups at the start of a study. A parallel design means the assigned groups are compared over the trial rather than participants crossing through both strategies. Neither design label, by itself, supplies an estimate of the treatment contrast. In this record, a primary outcome estimate and its uncertainty are not reported.

What does an endpoint comparison require?

For a binary or count-based endpoint, a comparison requires clearly defined outcome data for each group and a stated analysis approach. The primary measure is described as participants using opioids at day 7, assessed through medication records and a urine drug test. However, the record identifies several categories or time points and does not present one primary comparison. The group counts, the exact contrast, and any adjusted or unadjusted estimate are not reported in the registry record. No effect can be reconstructed from the endpoint description alone.

In general, a confidence interval is used to express the statistical uncertainty around an estimated effect. A narrower interval indicates greater precision under the assumptions of the analysis, while a wider interval indicates less precision. A confidence interval also helps readers judge whether the data remain compatible with effects of different sizes and directions. No primary-outcome confidence interval is reported. A p-value, if reported, would address compatibility with a particular null hypothesis under a statistical model; it would not state the probability that the null hypothesis is true or explain the practical size of the effect. The registry record provides no primary-outcome p-value.

What does the open-label design imply?

The trial is recorded as having no masking. In general, when participants and care teams know the assigned strategy, expectations or treatment decisions can influence outcomes, particularly outcomes involving symptom experience or care use. Medication records and urine testing are objective sources for assessing opioid use, but the record does not specify how the two sources were reconciled or whether assessors were masked. This is a consideration for interpretation, not evidence that the endpoint was biased.

How should adverse-event counts be read?

The serious-event and other-event figures are descriptive counts among the participants listed as at risk in each group. Counts alone do not provide a formal comparison, and the registry record gives no uncertainty interval or statistical test for these figures. In general, adverse-event interpretation also depends on how events were defined, collected, graded, and followed. Those details, as well as event terms for the other events, are not reported in the registry record. Zero reported serious events or deaths in an arm should be read as a registry count, not as proof that an event is impossible or that no event could occur outside the reporting period.

What do the planning assumptions mean?

The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. It is explicitly a planning illustration based on the observed effect, not the trial’s own design justification. Such illustrations describe hypothetical sample-size requirements under stated assumptions; they are not observed power and do not demonstrate that the trial had adequate power. The numerical planning outputs and the trial’s own sample-size justification are not reported in the registry record.

In general, a planning calculation depends on the outcome definition, the effect considered important to detect, the variability or event frequency, the chosen error rates, and the analysis model. If any assumption differs from the eventual data or planned analysis, the illustration may not match the actual precision achieved. Because the primary result and its analysis are not reported, the planning illustration cannot be used to infer the trial’s observed effect or certainty.

The record lists 0 analyses. This means there are no analysis results in the registry record to assess; it does not establish whether analyses were conducted elsewhere or whether additional results will be posted. Any interpretation should keep that distinction clear.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes a primary outcome with several categories or time points and does not reduce it to one comparison. It also lists five outcome measures. When a study evaluates multiple outcomes, time points, or categories, the chance of at least one apparently notable result can increase if each is tested separately. In general, a prespecified testing hierarchy or multiplicity adjustment can help control that issue, but the statistical plan for handling multiple comparisons is not reported in the registry record.

The registry lists 0 analyses, and no primary outcome estimate or uncertainty measure is reported. It is therefore not possible to identify which comparison, if any, was treated as the main inferential test, whether tests were adjusted, or whether analyses were exploratory. The record also does not report interim analyses or stopping rules. Their absence from the registry record does not establish whether they were or were not used.

Missing-data methods and analysis populations are also not reported in the registry record. There is no description of how participants with unavailable day-7 medication records or urine tests were handled, whether any imputation was planned, or whether the primary analysis followed randomized assignment. The record does not provide participant flow or endpoint-specific denominators for the primary outcome. These details matter because exclusions or incomplete outcome ascertainment can affect the interpretation of a group comparison.

In general, an intention-to-treat analysis compares participants according to their randomized assignment, while other analysis populations can apply additional eligibility or adherence rules. The registry record does not identify an analysis population, so it would be inappropriate to assume one. Without the comparison definition, multiplicity approach, missing-data handling, and analysis population, the primary endpoint cannot be independently evaluated from the posted results.

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.

Most frequent non-serious adverse event terms

The registry reports 0 serious adverse events among 151 participants at risk in the acupuncture plus usual-care group and 0 among 147 at risk in the usual-care group. It reports 0 deaths in each group. For other adverse events, the reported figures are 39 participants affected among 151 at risk with acupuncture plus usual care and 0 among 147 at risk with usual care.

These are registry counts, not a complete account of the events or a statistical comparison. The record does not list serious-event terms, and it does not provide event descriptions for the other adverse events. It also does not report the event-collection period, severity grades for other events, or an analysis comparing groups. Therefore, the figures alone cannot explain the difference in reported other-event counts or establish whether it reflects treatment, ascertainment, or another factor.

In general, safety counts should be interpreted in light of definitions, follow-up duration, completeness of reporting, and the number of participants monitored. A count of zero means no events were recorded in that category in the registry results; it does not establish that the underlying risk is zero. These safety figures are separate from the unreported primary opioid-use comparison and cannot answer the trial’s primary question.

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

The registry record makes clear what OPTIMAL-HiChemo set out to compare: usual pain management with acupuncture added versus usual pain management alone during high-dose chemotherapy for people with myeloma or lymphoma. It identifies opioid use at day 7 as the primary endpoint and describes medication records and urine testing as assessment methods. It also gives descriptive adverse-event counts.

What the record does not provide is a single primary outcome comparison. The day-7 opioid-use counts by group, an effect estimate, and measures of statistical uncertainty are not reported. As a result, the available information cannot show the direction, size, or precision of a difference in opioid use. It also cannot establish whether any difference would be attributable to the assigned strategy under the trial’s analysis.

The reported adverse-event counts should not be treated as a substitute for the primary result or a full safety analysis. Serious adverse events and deaths are recorded as zero in both groups, while other adverse events are recorded for 39 participants in the acupuncture plus usual-care group and 0 in the usual-care group. The registry does not describe the other events or provide a formal comparison. Those counts do not, by themselves, identify a cause or provide a complete characterization of safety.

In general, a randomized trial can inform a comparative question when its outcome definitions, group results, analysis methods, and uncertainty are reported. The design information is useful for understanding the intended comparison, but design alone does not determine the result. The record therefore supports neither a claim that acupuncture reduced opioid use nor a claim that it did not. It describes the trial question and selected reported counts, while leaving the main comparative result unresolved in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically interesting because its primary question concerns opioid use within a defined supportive-care strategy, rather than a comparison between pain treatment and no treatment. Both groups receive usual care, and opioid medication remains available in either group. The contrast is therefore the addition of acupuncture to usual care, not the removal of established pain management from one arm.

The endpoint combines a clinically relevant behavior—opioid use—with a specified assessment time and more than one information source. That makes clear outcome definitions and reporting important. Readers need to know how use was determined from medication records and urine testing, which time point or categories formed the main comparison, and how incomplete measurements were handled. Those details and the primary result are not reported in the registry record.

The unmasked design also makes interpretation methodologically important. In general, knowledge of assigned treatment may affect care decisions, participant experience, or reporting. A randomized design can still provide a useful comparison, but readers need transparent information about outcome assessment, analysis populations, and potential departures from assignment. The registry record does not provide those analysis details.

Finally, the reported adverse-event counts illustrate why raw counts require context. Serious events and deaths are recorded as zero in both groups, while other adverse events are reported in one group and not the other. Without event terms, follow-up details, and comparative uncertainty, these figures are descriptive rather than a complete inferential safety assessment. The trial’s statistical value to readers depends on a fuller report of the primary comparison and its precision, together with methods that clarify how outcomes and missing observations were handled.

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.

A central limitation of the available registry information is that it does not report the primary opioid-use result. The endpoint description identifies day 7 and the assessment sources, but there are no group-specific primary counts, effect estimate, confidence interval, or p-value. The outcome is also described as having several categories or time points without one comparison selected in the posted results. This prevents assessment of the primary contrast’s direction, magnitude, or precision.

The record does not describe how opioid use was classified when medication records and urine tests might not agree, or how the endpoint was handled when either source was unavailable. Missing-data methods, analysis populations, participant flow for the primary endpoint, and protocol deviations are not reported. Nor does the registry explain the randomization sequence, allocation concealment, usual-care implementation, or masking of outcome assessment.

The safety information has additional limits. Serious adverse-event counts and deaths are reported, but serious-event terms are not listed. Other adverse events are reported as counts without event descriptions or a statistical comparison. The registry record does not specify the safety follow-up period or provide enough detail to interpret the difference in other-event counts.

Although a planning illustration is described, it is based on the observed effect and is not the trial’s own design justification. The registry record does not report the numerical planning outputs or its original sample-size rationale. It also does not report a multiplicity strategy or interim-analysis plan. These limitations describe gaps in the registry record and do not establish what was included in the full protocol or other reporting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Managing Pain and Symptom Burden Caused by Chemotherapy in People With Myeloma or Lymphoma — NCT04459416.
• Registry record last updated 2026-10-09; status last verified 2026-10.
• Results first posted 2024-12-04.
• 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

OPTIMAL-HiChemo is a randomized, parallel-group, phase 3 trial with no masking, sponsored by Memorial Sloan Kettering Cancer Center. The registry lists an enrollment of 299 and includes people with multiple myeloma, Hodgkin disease, or non-Hodgkin lymphoma. Its status is active, not recruiting.

The trial compares acupuncture plus usual pain management with usual pain management alone. Its primary endpoint concerns opioid use at day 7, assessed through medication records and a urine drug test. The registry does not report a single primary comparison or its numerical result. It reports 0 serious adverse events and 0 deaths in each group; other adverse events are reported for 39 participants in the acupuncture plus usual-care group and 0 in the usual-care group. Event details and comparative analyses are not reported in the registry record.