Auranofin in Decreasing Pain in Patients With Paclitaxel-Induced Pain Syndrome: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Auranofin in Decreasing Pain in Patients With Paclitaxel-Induced Pain Syndrome (NCT02063698), a randomized phase 2 study. The primary outcome is Count/Percentage of Patients Who Report Having Experienced the Paclitaxel-induced Pain Syndrome (PIAPS) for One Week After Paclitaxel After Enrollment to the Current Trial, Assessed by the Modified Brief Pain Inventory Scale (BPI).

2. Clinical Question

The question is about the frequency of participants meeting the registry’s pain-reporting definition, rather than a comparison of average pain scores. The record describes the study as a pilot randomized, placebo-controlled test of auranofin. Its stated rationale is to assess whether auranofin can decrease pain following paclitaxel in patients with a history of paclitaxel-induced pain. The registry record does not report a conclusion about the treatment effect.

3. Trial Design

NCT02063698 is a phase 2 randomized, double-masked, parallel-group pilot trial sponsored by Mayo Clinic. The record lists enrollment of 30 participants and marks the study as completed. Its listed start date is 2014-02-19, and its primary completion date is 2015-11-11. These registry entries describe the trial’s status and design; they do not establish how many participants contributed data to a particular outcome.

Participants were assigned to an auranofin arm or a placebo arm. The arm descriptions state that both treatments were given by mouth on day 2. The study also lists questionnaire administration as an intervention. The brief summary identifies the population of interest as patients who had previously experienced paclitaxel-induced pain and describes the assessment as pain following paclitaxel.

The primary outcome was framed as a per-arm count and percentage of participants reporting the specified pain experience for one week after paclitaxel. Pain was assessed using the modified Brief Pain Inventory, with daily worst-pain ratings described for day 2 through day 8. The primary outcome timeframe is listed as up to 28 days. Secondary outcomes include normalized area under the curve for average pain, toxicity assessed using NCI CTCAE version 4, symptom-summary measures, and pain-location measures. The record lists 9 outcome measures and 14 analyses.

The record does not report the randomization sequence method, allocation concealment procedures, the details of masking, or the planned sample-size justification. It also does not report protocol deviations or a participant flow account. These omissions limit what can be inferred about how the design was implemented and which participants contributed to each analysis.

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 Count/Percentage of Patients Who Report Having Experienced the Paclitaxel-induced Pain Syndrome (PIAPS) for One Week After Paclitaxel After Enrollment to the Current Trial, Assessed by the Modified Brief Pain Inventory Scale (BPI), measured over Up to 28 days.

The primary endpoint counts participants who reported experiencing the paclitaxel-induced pain syndrome for one week after paclitaxel following enrollment in the trial. The registry describes daily worst-pain ratings using a question from the modified Brief Pain Inventory. The endpoint groups ratings into less than 4 and greater than or equal to 4 for each day from day 2 to day 8. The modified Brief Pain Inventory is described as ranging from 0 to 10, with higher scores corresponding to more or worse pain.

A count-based endpoint represents how many participants meet the stated reporting criterion in each arm. The registry also describes reporting a percentage, but the arm-specific counts and percentages are not reported in the registry record. The record says Fisher’s exact test will be used to compare the frequency of participants experiencing the syndrome between arms. No test result is reported in the registry record.

Using a defined pain threshold can make a patient-reported symptom easier to interpret as a frequency, but it does not preserve all the information in each pain rating. Ratings on either side of the threshold are treated as different categories, while ratings within a category are not distinguished by this endpoint. The registry also lists average-pain and symptom-summary outcomes, which address other aspects of pain. Their results are not reported in the registry record.

The endpoint is relevant to the trial’s stated question because it focuses on reported pain during the period after paclitaxel. It does not, by itself, describe pain severity across the full rating scale, duration beyond the assessment window, or the experience of every participant who received treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical methods described in the registry concern a binary, participant-count outcome. A participant is classified according to whether the stated pain-reporting criterion is met. The primary endpoint description calls for a count and percentage in each arm and names Fisher’s exact test for comparing the frequency between arms. The registry record does not report the result of that test or the underlying primary counts.

What does a count-based endpoint represent?

A count-based endpoint describes how many participants meet a defined outcome. When accompanied by a denominator, it can also be expressed as a proportion or percentage. For this trial, the intended outcome is the frequency of participants reporting the specified paclitaxel-induced pain syndrome. Counts can be straightforward to interpret, but they do not show the full distribution of pain ratings. In particular, a threshold-based classification does not distinguish among ratings that fall into the same category.

The endpoint description refers to ratings less than 4 and greater than or equal to 4 on the modified Brief Pain Inventory. This is a categorization of a pain rating, not a comparison of average scores. The registry says the scale ranges from 0 to 10 and that higher scores indicate more or worse pain. It does not report how participants with incomplete daily ratings were handled when deriving the week-long endpoint.

Why name Fisher’s exact test?

In general, Fisher’s exact test is a method for assessing whether the distribution of a binary outcome differs between groups. It uses the observed counts to evaluate the evidence against a null hypothesis of no association between group assignment and outcome classification. It is often considered for categorical data, especially when the available counts are limited. This general explanation describes the method, not a result from this trial.

The registry states that Fisher’s exact test will be used for the primary comparison. It does not report the test statistic, p-value, or confidence interval. A p-value, if reported, would address how compatible the data are with a specified null model; it would not by itself measure the size or practical importance of a difference. A confidence interval, if reported, would communicate the range of effect values compatible with the data under the method used. Neither is reported for the primary comparison in the registry record.

How should uncertainty be considered?

General statistical interpretation should consider both the estimated effect and its uncertainty. Counts from a pilot trial can be imprecise, particularly when there is limited information for a binary outcome. A lack of a small p-value would not establish equivalence, and a small p-value would not automatically establish a clinically important effect. The registry record does not provide the primary effect estimate or uncertainty interval, so the precision of the comparison cannot be assessed.

The enrollment listing is 30, but it is not a substitute for outcome-specific denominators. Participants may not all contribute data to every assessment, and the record does not state the number analyzed for the primary endpoint. The analysis population, handling of missing outcomes, and any imputation procedure are not reported in the registry record. Without those details, the relationship between enrollment and the information used in the primary analysis is unclear.

What do the sample-size illustrations mean?

In general, sample-size calculations based on an observed effect are planning illustrations. They describe the number of participants per arm that would be associated with stated design assumptions and a chosen target effect. They are not observed power, and they do not prove that the trial was adequately powered or that a future study will reproduce the effect.

The record’s sample-size assumptions describe a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. The effect to detect is described as a stated fraction of the observed effect. The record further distinguishes participant-per-arm quantities from total event quantities for time-to-event outcomes. Those assumptions are not a substitute for the trial’s own sample-size justification, which is not reported in the registry record. Numerical planning estimates are not reported in the registry record.

Why are multiple outcomes relevant?

The record lists several outcomes, including average pain, toxicity, symptom-summary measures, and pain locations. When many outcomes or analyses are considered, the chance of observing an apparently notable result by chance can increase. In general, multiplicity procedures can address this issue, but they depend on which outcomes are considered confirmatory and how comparisons are organized. The registry record does not report a multiplicity adjustment or a statistical plan specifying how to interpret results across the listed outcomes. It also does not report the secondary outcome results.

These method descriptions explain how the stated endpoint and test are generally understood. They should not be mistaken for evidence that a particular result was obtained. The registry record supplies no primary effect estimate, primary p-value, or primary confidence interval with which to assess the treatment comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 9 outcome measures and 14 analyses, including a primary pain endpoint and secondary measures of average pain, toxicity, symptoms, and pain location. The primary endpoint description covers several threshold categories or time points, and the record does not reduce those assessments to a single reported comparison. This range of outcomes makes it important to know which analyses were planned as primary or confirmatory and how results across analyses were to be interpreted.

The statistical plan for handling multiplicity is not reported in the registry record. No adjustment method, outcome hierarchy, or decision rule for interpreting several comparisons is described. In general, when multiple outcomes are tested, the chance of at least one apparently unusual result can rise. That possibility is a reason to interpret individual comparisons in the context of the full analysis plan, but it does not show that any particular result is false or true.

Missing-data methods are also not reported in the registry record. The record does not describe the amount or pattern of missing pain assessments, how a participant with incomplete daily responses would be classified, or whether any imputation was planned or used. Outcome-specific denominators and the analysis population are not reported. It is therefore not possible to determine whether the primary analysis included all randomized participants or a defined subset.

The record does not identify an intention-to-treat, per-protocol, or other analysis population, and it does not describe sensitivity analyses for missing data. These omissions matter because the analysis population and missing-data assumptions can affect the interpretation of a randomized comparison. No assumptions should be made about the trial’s analysis procedures beyond the Fisher’s exact test named for the primary comparison.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: febrile neutropenia (6.7%), abdominal pain (6.7%), urinary tract infection (6.7%), neutrophil count decreased (6.7%), arthralgia (6.7%).

The registry reports serious adverse events by arm. In the auranofin arm, 15 participants are listed as at risk and 2 as affected; in the placebo arm, 15 are listed as at risk and 5 as affected. Deaths are listed as 0 in each arm. These are descriptive registry counts, not proof of a treatment-related cause or a comparative safety effect.

The record also lists the most frequent serious adverse event terms with percentages of 6.7% each: febrile neutropenia, abdominal pain, urinary tract infection, decreased neutrophil count, arthralgia, and myalgia. The record does not provide further detail about the timing, severity beyond the serious classification, or treatment attribution for these terms. The listed percentages should not be interpreted as a complete account of all adverse events.

Other adverse events are reported as affecting 15 participants in each arm, with 15 at risk in each arm. Serious and other adverse events are separate categories in the registry record and should be read separately. The record does not provide event-level narratives, exposure-adjusted rates, or a formal comparative safety analysis. Because the trial is described as a pilot and the reported counts are descriptive, they do not by themselves establish whether one treatment is safer than the other.

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

The record establishes that a randomized, double-masked, placebo-controlled pilot trial was conducted to assess auranofin for pain following paclitaxel in patients with a prior history of paclitaxel-induced pain. It specifies the primary outcome definition and the intended comparison of event frequencies using Fisher’s exact test. It also reports some safety counts. These are meaningful features of the trial record, but they are not a report of the primary treatment effect.

The arm-specific primary pain counts, percentages, test result, effect estimate, and confidence interval are not reported in the registry record. It is therefore not possible to determine from this record whether the primary outcome differed between arms, how large any difference was, or how precisely it was estimated. The missing results should not be interpreted as evidence of benefit, no effect, or harm.

The endpoint concerns participants meeting a particular pain-reporting definition during the stated assessment period. It does not represent every dimension of pain, and a threshold-based count is not equivalent to a comparison of average pain ratings. The registry lists additional pain and toxicity outcomes, but their results are not reported in the registry record. Those measures cannot be used to confirm or contradict the primary outcome.

The study’s pilot designation and enrollment listing also require care in interpretation. Enrollment alone does not indicate the number analyzed for each outcome, and the record does not report the primary analysis population or missing-data methods. Nor does the record report the trial’s own sample-size justification. Any sample-size illustration based on an observed effect is a planning exercise under stated assumptions, not observed power and not a guarantee about a later study.

The serious adverse event counts are descriptive. They do not establish that an event was caused by a study treatment, and the registry record does not report a formal comparative safety analysis. In short, the record describes what the study set out to measure and gives limited safety information, but it does not contain the primary numerical efficacy results needed to draw a treatment-effect conclusion.

13. Why This Trial Matters Statistically

This trial is statistically notable for asking a focused question using a randomized, placebo-controlled design while defining its primary outcome as a participant-level frequency. That design aims to compare the proportion of participants meeting the stated pain criterion in the auranofin and placebo arms. The registry names Fisher’s exact test for that comparison, a method suited to categorical outcome data. The rationale and endpoint are described, but the primary numerical results are not reported in the registry record.

The endpoint also illustrates a common trade-off in clinical measurement. Turning a pain rating into a threshold-based category can make the outcome easier to express as a count, but it discards distinctions among ratings within each category. The record also lists average-pain and symptom-summary outcomes, which could capture different features of the experience. Because their results are not reported, it is not possible to assess how those measures relate to the primary endpoint.

The pilot setting highlights why statistical interpretation depends on more than the design label or enrolled group size. Precision depends on the observed data and the participants contributing to the analysis. The record does not report outcome-specific denominators, uncertainty intervals, or a sample-size justification. Its planning assumptions describe a sample-size illustration, not observed power.

The number of listed outcomes and analyses also makes transparency about the analysis plan important. Multiplicity and missing-data methods are not reported in the registry record. Such details help readers distinguish planned comparisons from exploratory ones and understand how incomplete assessments were handled. Here, their absence limits interpretation of any potential result, alongside the absence of the primary efficacy findings themselves.

For biostatistical readers, this record is a reminder that a trial’s question, design, outcome definition, and analysis method may be visible even when the estimates needed to answer the question are not. Statistical conclusions require the observed outcome data and information about how they were analyzed; design metadata alone cannot supply those conclusions.

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 interpreting this trial from the registry record is that the primary outcome results are not reported. The record does not give arm-specific counts or percentages, the Fisher’s exact test result, an effect estimate, or a confidence interval. Without these, neither the direction nor the magnitude and precision of the primary comparison can be assessed.

The registry describes a threshold-based primary endpoint using daily ratings from day 2 to day 8, but it does not report how incomplete daily assessments were handled or how the week-long outcome was derived for participants with missing responses. The outcome-specific denominators, analysis population, and missing-data methods are not reported in the registry record. These gaps prevent assessment of how much primary-outcome information was available and whether the analysis population matched the randomized groups.

Although multiple secondary measures are listed, their results are not reported in the registry record. The record lists 9 outcome measures and 14 analyses, but does not describe a multiplicity strategy or a hierarchy of outcomes. It therefore does not allow an assessment of consistency across endpoints or the context for interpreting several possible comparisons.

The registry record does not report the randomization sequence method, allocation concealment procedures, masking details, protocol deviations, or a participant flow account. The listed enrollment does not establish how many participants contributed to every outcome. The trial is described as a pilot, but its own sample-size justification is not reported. These limitations constrain assessment of implementation, precision, and generalizability. The safety counts are also descriptive and do not include enough information to establish attribution or a formal comparative safety effect.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Auranofin in Decreasing Pain in Patients With Paclitaxel-Induced Pain Syndrome — NCT02063698.
• Registry record last updated 2019-04-23; status last verified 2018-12.
• Results first posted 2019-04-23.
• 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

NCT02063698 is a completed phase 2 randomized, double-masked, parallel-group pilot trial sponsored by Mayo Clinic. The registry lists enrollment of 30 participants, with auranofin given by mouth on day 2 in one arm and placebo given by mouth on day 2 in the other. The trial concerns pain following paclitaxel among patients who had previously experienced paclitaxel-induced pain.

The primary endpoint is a count and percentage of participants meeting the stated pain-reporting definition, based on modified Brief Pain Inventory ratings. The record names Fisher’s exact test for the comparison. Arm-specific primary results and the test result are not reported in the registry record. Several secondary pain and toxicity outcomes are listed, but their results are not reported.

Safety information includes serious adverse event counts of 2 in the auranofin arm and 5 in the placebo arm, with deaths listed as 0 in each arm. These counts are descriptive. The record does not report the analysis population, missing-data methods, multiplicity strategy, or the trial’s sample-size justification.