A Study To Evaluate Pregabalin In The Treatment Of Moderate To Severe Chronic Bone Pain Related To Metastatic Cancer: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study To Evaluate Pregabalin In The Treatment Of Moderate To Severe Chronic Bone Pain Related To Metastatic Cancer (NCT00381095), a randomized phase 4 study. The primary outcome is Duration Adjusted Average Change (DAAC) From Baseline in Daily Worst Pain, Fixed Dosing Date to Day 28.

2. Clinical Question

In statistical terms, the trial set up a comparison between a randomized group receiving flexible-dose pregabalin and a randomized group receiving placebo. The key outcome was not simply a pain score at one visit: it summarized change across a specified period after dose adjustment had ended, with the measurement duration taken into account. That approach aims to represent the average change over the observation interval rather than relying on a single day. It does not, by itself, reveal whether the groups differed. A numerical estimate and a measure of its uncertainty would be needed to interpret the direction, magnitude, and precision of a comparative effect. Those primary comparison results are not reported in the registry record.

3. Trial Design

This was a randomized, double-masked, parallel-group, phase 4 trial. The registry lists enrollment of 152 participants and identifies pregabalin and placebo as the two drug interventions. In a parallel-group design, participants are assigned to one study arm and assessed within that assigned arm; the record describes no crossover. Random allocation is intended, in general, to reduce systematic differences between groups at the point of assignment. Masking is intended, in general, to limit the influence of expectations on treatment delivery or outcome assessment. The registry does not state which people were masked, how allocation was concealed, or how masking was maintained.

The study title and summary describe an assessment of flexibly dosed pregabalin for cancer-induced bone pain, including its analgesic efficacy and tolerability. The arm description identifies flexible dosing for pregabalin; the placebo arm description is blank. Thus, the record does not report detailed dose schedules, titration rules, concomitant-treatment requirements, or procedures for stopping or changing medication. These details matter for understanding exactly what treatment strategy was compared, but should not be inferred from the general description.

The trial began in 2006-12, had primary completion in 2010-10, and is listed as terminated. The registry record does not state the reason for termination or explain how termination affected recruitment, follow-up, or analysis. It lists 152 participants enrolled, but does not give a breakdown of randomized participants by arm in the primary-outcome results presented in the record. Safety denominators are reported separately as 72 for pregabalin and 80 for placebo for the adverse-event groupings.

The primary outcome was duration-adjusted average change in daily worst pain from the fixed dosing date to day 28 or early termination. The listed secondary outcomes cover pain over additional intervals, pain severity and interference, average pain at successive weeks, and opioid or morphine-equivalent daily dose changes. These outcomes broaden the clinical description, but no numerical findings for them are included in the registry information summarized in the record. The registry also reports 13 outcome measures and no analysis entries. That means the outcome list should not be treated as a complete account of every analysis performed.

Although randomization and masking support a controlled comparison in principle, their presence does not replace reporting the outcome estimates, analysis populations, and uncertainty. Without those results, the design can be described, but the comparative primary-outcome finding cannot be reconstructed from the enrollment total or the safety counts.

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:

Analysis population for the primary outcome, as defined in the registry: Intent-To-Treat population (ITT): all randomized participants for whom at least one post-baseline efficacy evaluation was obtained; N= the number of participants with evaluable data analyzed; n= number of participants with evaluable data at the specific time point.

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 Duration Adjusted Average Change (DAAC) From Baseline in Daily Worst Pain, Fixed Dosing Date to Day 28, measured over Baseline, Fixed Dosing Date to Day 28 or Early Termination (ET).

The primary endpoint was duration-adjusted average change from baseline in daily worst pain, assessed from the fixed dosing date to day 28 or early termination. Pain was rated at the reference site using an 11 point Numeric Rating Scale, where 0 meant no pain and 10 meant the worst possible pain. The endpoint is described as the area under the curve of change in worst pain divided by the duration of pain measurement. In general, an area-under-the-curve summary combines measurements across an interval; dividing by the measurement duration expresses that accumulated change as an average over the observed period.

The fixed dosing date was defined as the last day that dose adjustment was needed. Anchoring the primary interval there focuses the measure on the period after dose adjustment, rather than mixing dose-adjustment and later observation into one summary. In general, adjusting for duration can be useful when follow-up intervals differ, because the average is scaled to the time observed. It does not eliminate all consequences of missing or early-terminated observations, and the registry record does not describe how those situations were handled analytically.

The endpoint is a continuous measure, and the registry identifies the planned summary as a mean with standard deviation. A mean describes the average observed change; a standard deviation describes how spread out individual measurements are around that mean. The primary outcome definition specifies change as the value at a week minus baseline. However, the posted results do not give a single numerical primary comparison, group means, standard deviations, or an estimate of the difference between groups. The endpoint definition therefore explains what was intended to be measured, not what the trial found.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary measure summarize?

The primary endpoint is a continuous measure. Its stated summary is a mean, accompanied by a standard deviation. In general, a mean gives the arithmetic average of measured values in a group. A standard deviation describes variation among individual values around that average. Neither statistic alone describes the difference between randomized groups; interpreting the comparison requires group-level estimates or a direct contrast. Those numerical primary results are not reported in the registry record.

The endpoint is duration-adjusted average change in worst pain. The registry defines it using the area under the curve of change in pain, divided by the duration of measurement. In general, an area under a curve aggregates measurements over time, so the result reflects more than a single assessment. Dividing by the observed measurement duration expresses that accumulated quantity as an average over the interval. This can make the summary less dependent on the length of observation, but it does not guarantee that participants with different follow-up patterns are directly comparable. The handling of differing observation durations and early termination is not reported in the registry record.

Why is a group comparison important?

Random allocation sets up a comparison between the pregabalin and placebo groups. In general, comparing randomized groups helps distinguish changes associated with assignment from changes that could occur over time in either group. A change from baseline within one arm is not itself a treatment effect: symptoms may change for reasons unrelated to the assigned intervention. The statistical contrast between groups is the relevant estimate for the randomized comparison. The posted primary results do not provide that contrast as one numerical comparison.

The trial is described as double-masked. In general, masking can reduce the influence of expectations on participant reporting, clinical interactions, or assessment. The record does not identify exactly who was masked or describe procedures for maintaining masking. It is therefore possible to describe the design label, but not to evaluate the practical success of masking from the registry information.

What does the scale contribute?

The Numeric Rating Scale used for worst pain ranges from 0, no pain, to 10, the worst possible pain. The primary outcome concerns change from baseline in this rating. Because the endpoint is based on repeated assessment over a period, it can represent average change across that period rather than change at one assessment alone. The registry specifies the reference site and the interval from the last day dose adjustment was needed to day 28 or early termination. It does not report the group means, standard deviations, or the numerical contrast needed to understand the observed scale changes.

In general, a confidence interval communicates uncertainty around an estimated effect. A p-value, when reported, addresses the compatibility of the data with a specified statistical null model; it does not quantify clinical importance or prove that a result is true or false. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record. The absence of these results prevents evaluation of statistical precision or inferential strength.

How should dispersion and over-dispersion be understood?

For a continuous outcome, the registry’s stated dispersion measure is the standard deviation. In general, greater spread among participant measurements can make a group mean less precise, particularly when the sample is limited. Over-dispersion is a concern in settings where observed variability exceeds what a chosen model assumes. In general, ignoring over-dispersion can lead to uncertainty estimates that are too small. The primary endpoint is identified as continuous with a mean and standard deviation, but the registry record does not describe a model, any over-dispersion assessment, or a variance adjustment. No claim about whether over-dispersion was present can be made from the endpoint description alone.

What are the planning calculations for?

Any sample-size figures described as planning illustrations use the observed effect as a reference and are not the trial’s original design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such calculations are hypothetical planning exercises. They do not describe the number of participants originally required by the protocol, and they are not observed power. The registry record does not report the original sample-size justification or the planned target enrollment rationale.

In general, power is a design-stage probability of detecting an effect under specified assumptions. A post hoc calculation based on an observed estimate does not establish whether a completed study was adequately powered, and it cannot replace reporting the estimated effect and its uncertainty. For this trial, the primary numerical result is not available as a single comparison, so the planning framework should not be interpreted as a substitute for the trial’s primary analysis.

What can be inferred from analysis reporting?

The registry lists 13 outcome measures and zero analysis entries. This distinction matters: an outcome definition states what was intended to be measured, while an analysis entry would describe a result or analysis detail. The listed outcomes include several pain summaries, pain interference and severity measures, and opioid-dose measures. The record does not provide enough analysis detail to establish the statistical model, covariate adjustment, multiplicity strategy, or sensitivity analyses. Those features should not be inferred from the design labels or endpoint wording.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 13 outcome measures, including a primary pain outcome and secondary measures covering pain at different intervals, pain severity and interference, average pain, and opioid or morphine-equivalent dose. When a study assesses multiple outcomes or time points, there are generally multiple opportunities to observe apparently notable findings. In general, multiplicity methods can control or describe the risks associated with making many statistical comparisons. The registry record does not report a multiplicity adjustment, a hierarchy of confirmatory tests, or another strategy for interpreting multiple outcomes.

The record also notes that the primary outcome has several categories or time points and was not reduced to one comparison. This prevents a straightforward account of one primary estimate. The statistical analysis plan, including how the endpoint’s categories or time points were intended to be combined or tested, is not reported in the registry record. No result should be selected from among possible time points as though it were the sole primary finding.

The defined Intent-To-Treat population includes all randomized participants for whom at least one post-baseline efficacy evaluation was obtained. The registry distinguishes the analyzed N, meaning participants with evaluable data, from n at a specific time point. This makes clear that evaluable sample sizes can vary by analysis or time point. However, the record does not give primary-outcome sample sizes at each time point or describe imputation, exclusion, or other missing-data methods. It is therefore not possible to assess whether missing observations could have influenced the primary result.

The trial is listed as terminated, but the reason for termination and any resulting changes to follow-up or analysis are not reported in the registry record. The absence of analysis entries also limits assessment of which planned analyses were completed. These reporting gaps do not establish that a particular method was or was not used; they mean its use cannot be evaluated from the registry information.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: disease progression (5.6%), anaemia (2.8%), pneumonia (2.8%), neoplasm progression (2.8%), device dislocation (1.4%).

The registry reports serious adverse events affecting 12 of 72 participants in the pregabalin group and 12 of 80 in the placebo group. For other adverse events, it reports 38 of 72 in the pregabalin group and 31 of 80 in the placebo group. These are counts and denominators for the specified groupings. They should be read as descriptive safety information, not as evidence about the primary pain outcome.

The listed serious adverse-event terms are Disease progression, 5.6%; Anaemia, 2.8%; Pneumonia, 2.8%; Neoplasm progression, 2.8%; Device dislocation, 1.4%; and Lower respiratory tract infection, 1.4%. The registry information does not identify an arm-specific incidence for each listed term. These percentages should therefore not be attributed to one group unless the record makes that attribution. Death counts are not reported in the registry record.

In general, adverse-event counts describe events recorded during the study, but interpretation depends on definitions, ascertainment, follow-up, and participant exposure. The registry record does not give detailed information on these points, nor does it report a statistical comparison or uncertainty interval for the safety counts. The counts alone do not establish causation or comparative risk. They should be read alongside the limited reporting of event definitions and the absence of the primary efficacy comparison, rather than as a substitute for either.

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

The record describes a randomized, double-masked comparison of flexible-dose pregabalin and placebo for cancer-induced bone pain. It specifies a primary measure based on duration-adjusted average change in daily worst pain, using an 11 point Numeric Rating Scale and an interval beginning at the fixed dosing date. This gives readers a clear outline of the intended primary question and the kind of outcome measured.

However, the posted results do not report one numerical primary comparison. The registry notes multiple categories or time points and does not reduce them to one comparison. There are no reported primary group means, standard deviations, effect estimate, confidence interval, or p-value in the record. As a result, the size, direction, and precision of the comparative pain outcome cannot be determined from the registry record. The endpoint description is not itself an outcome finding.

The safety section gives counts for serious and other adverse events, along with selected serious-event terms and percentages. These figures describe recorded events, but do not establish that an event was caused by a study intervention, and the record does not provide uncertainty estimates for comparisons. The serious-event term percentages are not reported by arm in the information summarized, so they should not be assigned to either treatment group.

The registry’s terminated status is also a fact about the trial record, but the reason for termination and its consequences are not reported. It does not by itself show that the trial was stopped for a particular outcome, that follow-up was incomplete, or that its findings favored either arm. Similarly, the enrollment total and safety denominators do not reveal the number included in each primary-outcome analysis.

In general, a treatment comparison is best interpreted using the estimated difference, its uncertainty, the analysis population, and the missing-data and multiplicity methods. Several of these details are not reported in the registry record. The defensible conclusion is therefore limited: the trial was designed to assess pain change in a randomized comparison, but the record does not present a single numerical primary result that would allow its comparative magnitude or precision to be judged. No clinical recommendation follows from this statistical description.

13. Why This Trial Matters Statistically

This trial is statistically notable because its central outcome is a longitudinal summary rather than a single pain score at one visit. The duration-adjusted average change uses pain measurements over the interval from the fixed dosing date to day 28 or early termination. In general, such summaries can capture the pattern across a period and account for measurement duration in the endpoint definition. They also make clear why the analysis needs transparent reporting about observation time and incomplete follow-up.

The study was randomized and double-masked, which are important design features for a controlled comparison. In general, randomization can help balance measured and unmeasured characteristics between assigned groups, while masking can limit some forms of expectation-related influence. These design properties support the logic of comparing the groups, but they do not guarantee that a result is unbiased or precise. Interpretation still depends on how the endpoint was analyzed, who was included, and how missing observations were handled.

The registry record highlights a distinction between a detailed outcome definition and a reported analysis. It describes the pain scale, measurement interval, and ITT definition, yet does not provide one numerical primary comparison. It lists multiple outcomes and says the primary outcome was not reduced to one comparison. This makes the reporting gap especially consequential: readers can understand what the investigators intended to measure, but cannot judge the effect estimate or its uncertainty.

The record also illustrates why safety counts and efficacy outcomes need separate interpretation. Serious and other adverse-event counts are reported, but they cannot answer the primary pain question. Nor can those counts replace estimates of uncertainty or a description of the analysis population. The terminated status adds context, while the absence of a reported reason cautions against attributing it to any particular result.

Statistically, the trial matters as an example of how design labels and endpoint definitions do not by themselves make a study’s result interpretable. A randomized design frames the comparison; outcome reporting supplies the evidence needed to evaluate it. Here, the record leaves the central comparative estimate unreported, so the appropriate emphasis is on that limitation rather than an inferred conclusion.

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 in interpreting this trial from the registry record is that the primary outcome is not reported as one numerical comparison. Although the endpoint is defined in detail, the record says it has multiple categories or time points and was not reduced to a single comparison. No primary group means, standard deviations, contrast estimate, confidence interval, or p-value are reported in the information summarized. The comparative effect and its precision therefore cannot be evaluated.

The registry does not report the analysis model, any covariate adjustment, the multiplicity strategy, or sensitivity analyses. It lists 13 outcome measures and zero analysis entries. Consequently, the relationship between the outcome list and the analyses actually conducted cannot be assessed. The absence of a reported approach should not be read as proof that no approach was used; the relevant details are not reported in the registry record.

The primary population definition requires at least one post-baseline efficacy evaluation among randomized participants. The record distinguishes the analyzed N from the number evaluable at a specific time point, but does not report the primary-outcome sample sizes or how missing measurements were handled. This limits assessment of whether observations were incomplete and whether the analyzed population differed across time points.

The trial is listed as terminated, but the reason, timing in relation to recruitment or follow-up, and consequences for analysis are not reported. The record gives enrollment of 152 but does not provide a primary-analysis breakdown by arm. Safety denominators are available, but these cannot be assumed to be the efficacy analysis denominators.

Additional design details are limited. The registry does not state who was masked, how allocation was concealed, or the exact flexible-dose schedule. It also does not describe background treatment or the handling of early termination within the endpoint calculation. These omissions prevent fuller assessment of implementation and analysis choices. They do not establish that the trial’s design or conduct was inadequate; they restrict what can be concluded from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study To Evaluate Pregabalin In The Treatment Of Moderate To Severe Chronic Bone Pain Related To Metastatic Cancer — NCT00381095.
• Registry record last updated 2021-01-20; status last verified 2019-04.
• Results first posted 2011-09-27.
• 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 identifies a phase 4, randomized, double-masked, parallel-group study of flexible-dose pregabalin versus placebo for cancer-induced bone pain. Enrollment was 152, and the trial is listed as terminated. The primary endpoint was duration-adjusted average change from baseline in daily worst pain, assessed from the fixed dosing date to day 28 or early termination on an 11 point Numeric Rating Scale.

The record lists 13 outcome measures and zero analysis entries. It does not report a single numerical primary-outcome comparison; the primary outcome is described as having several categories or time points without reduction to one comparison. The ITT population is defined as randomized participants with at least one post-baseline efficacy evaluation, but primary-outcome sample sizes and missing-data methods are not reported.

Safety counts are reported for serious and other adverse events, while deaths and the reason for trial termination are not reported in the registry record. The available record therefore describes the trial design, endpoint, and selected safety information, but does not establish the magnitude or precision of the primary pregabalin-placebo comparison.