Subcutaneous Lidocaine For Cancer-Related Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Subcutaneous Lidocaine For Cancer-Related Pain (NCT01384877), a randomized phase 2, phase 3 study. The primary outcome is Number of Participants With Reduction in Worst Pain Intensity or Reduction in 24hr Opioid Dose of at Least 30% Without Worsening of Pain Scores.

2. Clinical Question

The trial was intended to evaluate a short-term response to lidocaine in the context of cancer-related pain, using both pain intensity and opioid requirement as components of the clinical question. Its description defines a clinically useful response as either a 2-point reduction in worst pain on a 0–10 scale or a reduction in 24-hour opioid requirement of at least 30%. The primary outcome description also states that the pain reduction or opioid-dose reduction had to last a minimum of 7 days.

The registry’s descriptions are not fully aligned about how the composite is formed. The brief summary describes pain reduction without an increase in opioid requirement, or no decrease in pain with at least a 30% opioid reduction. The primary outcome description instead lists a pain reduction or an opioid-dose reduction of at least 30%. The exact operational rule used for the posted analysis is not reported in the registry record. Without outcome counts and a defined comparison, the direction and precision of the treatment contrast cannot be assessed.

3. Trial Design

The record describes a randomized, triple-masked, crossover study of subcutaneous lidocaine infusion and placebo (D5W) for chronic cancer-related pain. It lists the study phases as phase 2 and phase 3, and the status as completed. The official title calls the study double blind, while the registry’s masking entry says triple. These descriptions do not identify which parties were masked, so that detail is not reported in the registry record.

In a crossover trial, participants receive the study treatments in a sequence rather than remaining in a single treatment group throughout. The study summary says participants received either lidocaine or placebo, followed at least 1 week later by the alternate agent. The arm descriptions refer to placebo first compared with lidocaine first, consistent with sequence-based treatment assignment. The registry record does not report the randomization method, the number assigned to each sequence, or whether treatment order was balanced.

The planned clinical question concerned response within 48 hours of infusion and persistence for a minimum of 7 days. The primary outcome timeframe is listed as 7 days. The interval between treatments was at least 1 week, but the rationale for that interval and any formal washout criteria are not reported in the registry record. A crossover design can allow each participant to contribute experience under both treatments, but interpretation depends on the sequence, completeness of measurements, and whether effects of the earlier treatment carry into the later period.

The record lists enrollment of 33. It states that participants were included in the primary analysis if they completed both treatment periods and all data were collected for both periods. The number meeting that criterion is not reported in the registry record. The start date is 2011-12 and the primary completion date is 2017-12. These dates describe the study timeline, not the duration of treatment effect or follow-up for each participant.

The sponsor is the British Columbia Cancer Agency. The registry lists quality-of-life questions as secondary outcomes, covering pain, other symptoms, anxiety or worry, communication with family or friends, depression, self-regard, and time spent on healthcare appointments. The results for these outcomes are not reported in the registry record.

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: One (1) participant signed the informed consent form but withdrew from the study before receiving any treatment.

Treatment 1

Treatment 2

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants were included in analysis if they completed both treatment periods and all the data was collected for both treatment periods

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: The overall number in the baseline analysis include all participants who signed the informed consent form. One (1) participant included in this analysis withdrew before receiving any treatment.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Reduction in Worst Pain Intensity or Reduction in 24hr Opioid Dose of at Least 30% Without Worsening of Pain Scores, measured over 7 days.

The primary outcome is a binary participant-level measure: whether a participant met the specified response criterion. The outcome title refers to a reduction in worst pain intensity or a reduction in 24-hour opioid dose of at least 30% without worsening pain scores. The detailed description identifies a 2-point reduction in worst pain over the last 24 hours compared with baseline, or at least a 30% reduction in 24-hour opioid dose, with the response lasting a minimum of 7 days. The record states that the assessment concerns a reduction in cancer pain within 48 hours of infusion.

A composite outcome can represent more than one route to a clinically relevant change. This is useful when improvement may appear as reduced pain, reduced opioid requirement, or a specified combination of those outcomes. It also means the binary result does not, by itself, show which component drove a response. Separate component results would be needed to distinguish a change in pain scores from a change in opioid dose.

The descriptions of the composite differ. The brief summary requires pain reduction without increased opioid use, or no decrease in pain with at least a 30% opioid reduction. The detailed primary outcome description presents the criteria differently. The exact rule used to classify participants is not reported in the registry record. The record also gives no primary outcome counts or estimated comparison, so the frequency of response and its precision cannot be determined from the registry information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The following statistical concepts are general explanations of how to interpret a randomized crossover study and a binary composite outcome. The registry record does not report the statistical analysis plan, the model used, or an inferential result for the primary outcome.

What does a binary endpoint represent?

A binary endpoint classifies each participant as meeting or not meeting a defined response criterion. The primary outcome in this record is described as a count of participants with a response, rather than a continuous change in pain score. Such a measure can make a clinical definition easier to interpret, but it compresses the underlying information. It does not show the amount of improvement beyond the threshold, the timing of changes within the assessment period, or which component of a composite was responsible for classifying a participant as a responder.

Composite outcomes need especially clear definitions. When a criterion can be met through alternative combinations of pain and opioid use, readers need to know the rule connecting those components. The registry’s brief summary and detailed primary outcome description differ in their wording. The analysis rule actually applied is not reported in the registry record. Without it, the outcome cannot be independently reconstructed from participant-level observations, even if those observations were available.

How does crossover allocation affect interpretation?

In a crossover design, participants receive each intervention in a sequence. This allows comparisons to be made within participants, which can reduce the influence of stable differences between participants. However, the design also makes treatment order and period important. Symptoms may change over time, and an earlier intervention may have effects that persist into a later period. These are general design considerations; the record does not establish that either issue affected this trial.

The study summary states that participants received lidocaine or placebo and later received the alternate agent, with at least 1 week between treatments. The record does not report the specific randomization procedure, the number assigned to each order, or the statistical approach to period and sequence. It also does not report a carryover assessment or criteria for deciding whether a participant’s later-period data could be used. Those details are important for understanding how the within-participant comparison was constructed.

What would a treatment estimate and confidence interval add?

A treatment estimate expresses the comparison in a chosen scale, while a confidence interval describes the statistical uncertainty around that estimate under the analysis assumptions. For a binary endpoint, a report might use a difference in response probabilities or another measure of relative comparison. These are general examples of possible methods, not claims about the method used in this study. The registry record reports none of these estimates for the primary outcome. Without an estimate and its uncertainty interval, readers cannot assess the magnitude or precision of the treatment contrast.

A p-value, if reported, would address how compatible the observed data are with a specified statistical null model under the analysis assumptions. It would not measure the probability that a treatment works, establish clinical importance, or replace an effect estimate. No primary p-value is reported in the registry record. The statistical plan, including any prespecified significance threshold for the primary comparison, is also not reported in the registry record.

Why does completeness of paired data matter?

The primary analysis population is described as participants who completed both treatment periods and had all data collected for both periods. This is a complete-case requirement for the crossover comparison. It can exclude participants who do not complete a period or lack measurements, and the characteristics of excluded participants may differ from those included. The number included, reasons for missing data, and methods for handling incomplete records are not reported in the registry record. Therefore, the extent and potential impact of missing data cannot be evaluated.

General approaches to missing data include analyses of observed complete cases, imputation, and sensitivity analyses under different assumptions about unobserved outcomes. These approaches answer questions under different assumptions; none can be attributed to this trial because the registry record does not report its missing-data methods. A full interpretation would need the analysis population, the missingness pattern, and the handling of incomplete treatment periods.

How should sample-size illustrations be understood?

The record describes a planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It also specifies that the effect to detect is a stated fraction of the observed effect. Such calculations estimate sample sizes for planning under their assumptions; they are not evidence of the study’s observed power. In this case, the primary observed effect and the resulting planning values are not reported in the registry information available for this analysis, so no sample-size conclusion can be drawn.

The record’s general note distinguishes planning quantities for ordinary outcomes from those for time-to-event outcomes. The primary endpoint is described as a binary participant count, not a time-to-event measure. The actual sample-size justification, target enrollment rationale, and any assumptions used when designing the trial are not reported in the registry record. A retrospective planning illustration should not be confused with the original design calculation.

What multiplicity issues arise?

The record lists multiple quality-of-life questions as secondary outcomes in addition to the primary outcome. When many outcomes are examined, the chance of at least one apparently unusual result can increase unless the analysis plan addresses multiplicity. This is a general statistical concern, not a statement that any secondary result was significant. The registry record does not report multiplicity adjustments, a hierarchy of outcomes, or results for the secondary questions. It also does not report the full set of analyses performed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary outcome and multiple secondary quality-of-life questions. These secondary measures address pain, other symptoms, worry, communication with family or friends, depression, self-regard, and time spent on healthcare appointments. When several outcomes are assessed, multiplicity is a general concern: examining many comparisons can increase the chance of finding an apparently noteworthy result by chance. The analysis plan for addressing that concern, if any, is not reported in the registry record. The record lists 0 analyses, and does not provide results for the secondary outcomes.

The primary analysis population is defined as participants who completed both treatment periods and had all data collected for both periods. This definition indicates that complete data across both periods were required for inclusion in that analysis. It does not give the number included, the reasons participants may have been excluded, or the extent and pattern of missing measurements. Those details are not reported in the registry record.

Missing data can affect a crossover comparison because complete paired information may not be available for every participant. General statistical approaches include complete-case analysis, imputation, and sensitivity analyses using alternative assumptions. The registry record does not report whether any of these methods were used, how incomplete treatment periods were handled, or whether any sensitivity analyses were conducted.

The record does not report whether there were interim analyses, a prespecified statistical plan, or a multiplicity procedure. It also does not report whether the primary outcome definition was changed during the study. These are not details that can be inferred from the completed status or the outcome descriptions. Without the analysis plan and outcome results, readers cannot assess how outcome selection, missingness, or multiple testing may have influenced the reported findings.

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 lists serious adverse event figures separately for lidocaine and placebo (D5W). For each group, 32 are listed as at risk and 0 as affected by serious adverse events. The record also lists other adverse events as affected in 3 for lidocaine and 2 for placebo. Deaths are listed as 1 for lidocaine and 2 for placebo. These entries are descriptive counts; they are not a comparative estimate of risk or a test of a treatment difference.

The record does not report the event descriptions, timing, severity categories beyond the serious-event distinction, or whether an event or death was considered related to treatment. In a crossover trial, participants may receive both treatments, so group labels alone do not explain how events were attributed across treatment periods. The method for assigning events to a treatment group is not reported in the registry record. The counts should therefore not be interpreted as proof that either treatment caused or prevented an event.

Zero serious events affected in a group does not demonstrate that serious harms are impossible; it describes the posted count within the registry’s reporting framework. The number of events and the level of detail are insufficient to characterize uncommon harms or compare safety precisely. No top serious adverse event terms are listed in the registry record. These safety entries should be kept distinct from the unreported primary pain outcome.

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

The record identifies a randomized crossover trial examining subcutaneous lidocaine infusion against placebo for cancer-related pain. Its primary question concerns a binary response involving worst pain intensity and 24-hour opioid dose, assessed in relation to a response within 48 hours and lasting at least 7 days. The study is listed as completed, and the record describes the requirement for complete data from both treatment periods for inclusion in the primary analysis.

Those design and endpoint details do not establish what the trial found. Primary response counts, an effect estimate, a confidence interval, and a p-value are not reported in the registry record. Consequently, the size and direction of any difference between lidocaine and placebo, and the precision of that comparison, cannot be determined from the information available. No conclusion about the treatment’s clinical benefit should be drawn from the outcome definition alone.

The composite itself also needs careful reading. The brief summary and detailed outcome description do not express the response rule in exactly the same way. Because the operational definition used in the analysis is not reported, the record does not make clear how different combinations of pain and opioid-use changes were classified. Even with a reported total response count, separate component results would help explain what the composite represents.

The safety counts are also limited. The registry lists no serious adverse events affected in either treatment group, along with other adverse events and deaths, but does not provide event details or attribution. These descriptive figures cannot establish the cause of events or provide a precise comparison of safety.

In short, the registry record provides useful information about the trial question, crossover structure, response definition, and selected safety counts. It does not report the primary efficacy results or sufficient analysis details to evaluate the treatment comparison. The absence of a result in this record should not be treated as evidence of no effect; it means the comparative result is not available in the registry information described.

13. Why This Trial Matters Statistically

This trial illustrates several statistical issues that arise when a clinical question is represented by a composite binary outcome. The study’s response definition combines pain intensity and opioid requirement, outcomes that capture different aspects of a patient’s experience and care. A composite can encode multiple routes to meeting a response threshold, but its interpretation depends on a precise rule for combining those components. The registry’s short and detailed descriptions differ, making the operational definition an important point to resolve before interpreting any response count.

The crossover design also affects the statistical question. Rather than comparing only separate groups of participants, a crossover study relies on observations from participants under both treatments. That can support within-participant comparisons, while also requiring attention to treatment order, period effects, and possible carryover. The registry record describes the alternate treatment after at least 1 week but does not report how these design features were handled in the analysis.

The stated analysis population highlights another key issue: the primary analysis required completion of both treatment periods and complete data for both. This may be a reasonable analysis definition, but interpretation requires knowing how many participants met it, why data were missing, and whether incomplete records were addressed in additional analyses. Those details are not reported in the registry record.

Finally, a completed-trial status and a detailed outcome definition are not substitutes for results. Without response counts, an effect estimate, and a measure of uncertainty, neither the magnitude nor the precision of the primary comparison can be judged. The record therefore serves as an example of why transparent reporting needs to include not only the design and endpoint, but also the analysis population, handling of missing data, and complete comparative results.

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 most consequential limitation of the registry information is that it does not report the primary outcome results. There are no response counts by treatment, comparative estimate, confidence interval, or p-value. The number of participants who met the complete-data analysis criterion is also not reported. Therefore, neither the efficacy contrast nor its precision can be evaluated.

The outcome definition is not fully consistent across the brief summary and the detailed primary outcome description. The former describes a composite involving pain reduction without increased opioid requirement, or no decrease in pain with at least a 30% opioid reduction. The latter describes a 2-point reduction in worst pain or at least a 30% reduction in opioid dose. The exact response rule applied in the analysis is not reported in the registry record. The lack of separate component results also prevents determining whether any response was driven by pain change, opioid change, or both.

The analysis population is restricted to participants who completed both periods and had all data collected for both periods. The number excluded under this criterion, reasons for noncompletion, missing-data methods, and sensitivity analyses are not reported. The registry record also does not report the statistical model, treatment-order allocation, handling of period effects, assessment of carryover, or prespecified analysis plan. These omissions limit assessment of how the crossover comparison was estimated.

The safety record contains counts but does not describe the events, their timing, or attribution. This limits interpretation of both serious events and deaths. The secondary quality-of-life outcomes are listed, but their results and any multiplicity approach are not reported. These limitations concern the registry information available and should not be taken as evidence that the full study report contains no further detail.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Subcutaneous Lidocaine For Cancer-Related Pain — NCT01384877.
• Registry record last updated 2019-07-12; status last verified 2019-04.
• Results first posted 2019-07-12.
• 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

NCT01384877 is a completed randomized, triple-masked crossover study of subcutaneous lidocaine infusion versus placebo (D5W) for cancer-related pain. The record lists phase 2 and phase 3, enrollment of 33, a start date of 2011-12, and a primary completion date of 2017-12. Participants received one treatment followed at least 1 week later by the alternate agent.

The primary outcome is a binary participant response involving worst pain intensity or 24-hour opioid dose, with a 7-day timeframe. The registry describes an analysis population requiring completion of both periods and complete data for both. It also lists quality-of-life questions as secondary outcomes.

Primary outcome results, the analyzed participant count, the statistical model, and missing-data methods are not reported in the registry record. Serious adverse event counts affected are listed as 0 in each group; other affected events and deaths are also recorded, without event details or attribution. The record therefore describes the trial’s design and intended measures but does not allow the primary treatment comparison to be assessed.