Safety and Efficacy of Buprenorphine Transdermal System (BTDS) in Subjects With Moderate to Severe Low Back Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Efficacy of Buprenorphine Transdermal System (BTDS) in Subjects With Moderate to Severe Low Back Pain (NCT00313014), a randomized phase 3 study. The primary outcome is Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12..

2. Clinical Question

3. Trial Design

This was a phase 3, randomized, parallel-group study of BTDS 20, BTDS 5, and oxycodone immediate-release in subjects with moderate to severe low back pain. The registry records triple masking. Its brief summary describes the treatment intervention as double-blind, so the record uses both descriptions; further details about who was masked are not reported in the registry record.

The planned double-blind treatment intervention lasted 12 weeks. The primary pain measure was collected at weeks 4, 8, and 12. Acetaminophen or ibuprofen was available as supplemental analgesic medication for all subjects, in addition to study drug. The record lists the patches as 5 mcg/h and 20 mcg/h, each applied for 7-day wear. The oxycodone immediate-release arm is described as 40 mg (two 5-mg capsules every 6 hours).

Enrollment is recorded as 660. The Full Analysis Population is also recorded as N = 660 and defined as randomized subjects who received at least one dose of double-blind study drug. These are distinct pieces of registry information; the record does not provide a participant flow account explaining exclusions, withdrawals, or the disposition of participants by treatment group.

The registry gives a start date of 2004-02, a primary completion date of 2005-09, and a status of terminated. The reason for termination and whether it affected planned recruitment, follow-up, or analyses are not reported in the registry record. The registry also lists an open-label run-in period, BTDS 10/20, in the safety data. Its role in the trial’s design and its relationship to the randomized treatment period are not described in detail.

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: Prerandomization: screening period \[Prospective assessment: subjects were assessed to ensure compliance with all inclusion/exclusion criteria\]. Opioid taper segment: assessed the severity of the subject's low back pain upon analgesic medication discontinuation. Open-label run-in period: identified subjects whose pain was controlled with BTDS 20.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Population (N = 660) consisted of subjects who were randomized and received at least 1 dose of double-blind study drug.

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 Average Pain Over the Last 24 Hours Score at Weeks 4, 8, and 12., measured over Last 24 hours score at weeks 4, 8, 12 of the double-blind phase.

The primary endpoint was the mean average-pain score over the last 24 hours, assessed at weeks 4, 8, and 12 of the double-blind phase. Subjects were asked about pain before study visits. The scale had 11 points, from 0, meaning no pain, to 10, meaning pain as bad as you can imagine. The registry identifies the outcome as a mean of a continuous measure and gives standard error as the dispersion measure.

A repeated pain score can describe how participants rate their recent pain during treatment, while comparing groups can estimate whether the recorded average differs between assigned treatments. A mean gives a group-level summary; it does not show how every participant responded. The standard error describes the precision of an estimated mean, rather than the spread of individual scores. General statistical interpretation should also consider the score’s scale and the time at which it was measured.

The registry lists several assessment times for the primary endpoint, rather than a single time point. It does not report the group means, standard errors, treatment contrasts, confidence intervals, or p-values for those assessments. Consequently, the magnitude, direction, and precision of any group differences cannot be described from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean summarize?

The primary outcome is identified as a mean, which is a way to summarize scores across a group. General statistical explanation: a mean gives a central group-level value but can conceal variation among participants. Two groups can have similar means while their individual scores vary substantially, or different means while many individual scores overlap. The registry record specifies standard error as the dispersion measure accompanying the mean. General explanation: standard error describes the precision of an estimated mean; it is not the same as the range or spread of individual participants’ scores.

The pain measure uses an 11-point scale with endpoints 0 and 10. General statistical explanation: the numerical difference between scores is often treated as meaningful for analysis of a continuous outcome, but a group mean does not preserve every feature of the score distribution. The registry record does not provide distribution summaries or the actual means, so distribution shape and the observed group-level values cannot be evaluated.

How should repeated assessments be understood?

The endpoint was assessed at weeks 4, 8, and 12. These assessments describe pain at several points during the double-blind phase. General statistical explanation: measurements from the same participant over time are related, so an analysis of repeated measurements may need to account for that within-participant correlation. The registry record does not report which model, if any, was used for these repeated assessments, whether each time point was tested separately, or whether a combined longitudinal analysis was performed.

Because the primary outcome is listed at multiple time points, interpretation requires knowing which comparison or summary was treated as primary for inference. The record does not supply a single contrast or a result for any listed time point. It also does not explain how values across visits were handled if participants missed a visit or stopped treatment.

What does randomization contribute?

Random allocation is intended to create treatment groups that can be compared without assigning treatment according to participants’ observed characteristics. General statistical explanation: randomization can support causal comparisons when allocation is maintained and outcome data are analyzed appropriately, but it does not guarantee identical groups in every sample or eliminate problems caused by missing data, deviations from treatment, or incomplete reporting. The registry records a randomized parallel design, but does not report the randomization sequence method, concealment details, or the analysis methods used to address departures from assigned treatment.

The registry describes triple masking and also calls the treatment period double-blind in its brief summary. Masking can limit some influences on care, reporting, and outcome assessment, depending on who is masked and how masking is maintained. The record does not identify the masked roles or describe whether masking was assessed. No further interpretation of the masking procedure is possible from the registry record.

What do confidence intervals and tests ordinarily add?

General statistical explanation: a confidence interval expresses uncertainty around an estimated effect, under the assumptions of the method used. Its width helps readers judge precision, while its position relative to a null value can help assess compatibility with no difference. A p-value, when reported, measures how surprising data at least as extreme as those observed would be under a specified null model; it is not the probability that the null hypothesis is true and does not measure the size or practical importance of an effect.

The registry record does not report confidence intervals, p-values, or estimated treatment contrasts for the primary outcome. No inferential result can therefore be interpreted, and no interval can be used to assess the precision of the comparison. The registry’s description of standard error for the outcome does not substitute for an uncertainty estimate for a between-group contrast.

Why can over-dispersion matter?

General statistical explanation: over-dispersion arises when observed variability is greater than a model assumes. If a model underestimates variability, its standard errors may be too small and its confidence intervals too narrow, making statistical evidence appear more precise than it is. This concept is especially relevant to outcomes whose variability is not well described by a simple model. The primary endpoint is described as a continuous mean, but the registry record does not report the model or distributional checks, so there is no basis for saying whether over-dispersion was assessed or relevant to the analysis.

What do planning illustrations mean?

General statistical explanation: sample-size planning uses assumptions about the effect to detect, variability, allocation, and error rates to estimate how many participants might be needed under a specified design. Such a planning calculation is not an observed result and does not establish the probability that a completed trial detected an effect. The registry’s planning description specifies a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as stated fractions of the observed effect. The description distinguishes participants per arm for non-time-to-event outcomes from total events for time-to-event outcomes.

Those assumptions are described as a planning illustration based on the observed effect, not as the trial’s own design. The record does not include numerical planning outputs in the information available for interpretation, and it does not report the trial’s sample-size justification. No planning estimate should be treated as observed power or as evidence about the primary outcome.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists four outcome measures and eight analyses. The primary pain outcome is assessed at weeks 4, 8, and 12, and the record indicates that it has several categories or time points rather than a single comparison. This creates an interpretation question: results from multiple time points or comparisons can increase the chance of a chance-positive finding if each is tested separately. General statistical explanation: multiplicity procedures can control or otherwise address that issue, but the registry record does not report whether any adjustment was planned or applied, nor does it specify a hierarchy among outcomes or time points.

The registry record does not report the analysis plan, the statistical tests for the primary endpoint, or which analysis was considered primary for inference. It does not state whether analyses were interim or final. No interim-analysis plan or conduct is reported in the registry record. The absence of such information does not establish that a particular procedure was or was not used.

The Full Analysis Population is defined as randomized subjects who received at least one dose of double-blind study drug. The record does not describe the handling of subjects who did not receive a dose, the handling of outcomes after treatment discontinuation, or whether other analysis populations were used. It also does not give the number of available pain scores at each assessment.

Missing-data methods are not reported in the registry record. There is no description of imputation, model-based handling of incomplete measurements, sensitivity analyses, or assumptions about why data might be missing. These details matter because conclusions can depend on how incomplete follow-up is addressed. Without outcome availability and missing-data methods, the potential influence of missing observations cannot be assessed.

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 4.50% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pancreatitis (0.9%), hematemesis (0.5%), intractable vomiting (0.5%), chest pressure (0.5%), acute cholecystitis (0.5%).

The double-blind safety summaries list subjects at risk and subjects affected by serious adverse events and other adverse events. In the BTDS 5 group, 6 of 221 were recorded with serious adverse events and 54 of 221 with other adverse events. In the BTDS 20 group, the corresponding counts were 7 of 219 and 118 of 219. In the oxycodone immediate-release group, they were 9 of 220 and 93 of 220. These are descriptive counts, not adjusted comparisons.

A separate open-label run-in period, BTDS 10/20, lists 10 of 1160 with serious adverse events and 389 of 1160 with other adverse events. Because this is identified as an open-label run-in group, it should be read separately from the double-blind treatment groups. The registry does not explain the relationship between the run-in population and the randomized groups.

The registry lists serious-event terms including pancreatitis at 0.9%, and hematemesis, intractable vomiting, chest pressure, acute cholecystitis, and pulmonary embolism each at 0.5%. Death counts are not reported in the registry record. The record does not provide event-level timing, exposure-adjusted rates, or statistical comparisons, so the counts alone do not establish a causal or comparative safety conclusion.

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

The trial record establishes the question that investigators intended to study: comparing BTDS 20 with BTDS 5 and oxycodone immediate-release among subjects with moderate to severe low back pain who were currently treated with oral opioids. It also describes a randomized, parallel, phase 3 design and a 12-week double-blind treatment period. The primary outcome was a pain rating collected at weeks 4, 8, and 12.

What the record does not establish is the comparative result for that outcome. Group means, standard errors, contrasts, confidence intervals, and p-values are not reported in the registry record. There is consequently no basis in this record for describing the direction or size of any pain difference, how precisely it was estimated, or whether an observed difference would be compatible with no difference. Missing outcome results must not be interpreted as showing equal outcomes or as showing a benefit or harm.

The adverse-event counts document reported safety summaries for the named groups. They do not, by themselves, establish that a treatment caused an event or that one treatment had a higher risk than another. Such conclusions would require careful attention to definitions, exposure and follow-up, event handling, and comparative analyses, which are not described in sufficient detail in the registry record.

The status is recorded as terminated, but the reason is not reported in the registry record. That status does not explain whether termination was related to safety, recruitment, operations, or another consideration. It also does not establish that the trial’s planned analyses were completed or identify changes to the study plan.

Accordingly, the registry record is useful for identifying the planned comparison, outcome definition, and available descriptive safety counts. It is not enough to determine whether the groups differed on the primary pain outcome or to draw a definitive comparative benefit-risk conclusion.

13. Why This Trial Matters Statistically

This trial illustrates why registration details and outcome results answer different statistical questions. The design record tells readers who the study concerned, which treatments were compared, and how the primary pain measure was defined. Those details help assess whether a reported result would address the intended clinical question. They do not reveal the result when the group estimates and contrasts are absent.

The endpoint has multiple assessment times, at weeks 4, 8, and 12. That makes the analysis plan important: separate tests, a chosen primary time point, and a combined repeated-measures analysis can answer different questions and may require different approaches to multiplicity and within-participant correlation. The registry does not report which approach was used. This is a reminder that knowing the measurement schedule is not the same as knowing the inferential strategy.

The record also distinguishes the Full Analysis Population from general enrollment and lists a separate open-label run-in safety group. Maintaining those distinctions matters for interpretation. A descriptive safety count in a run-in group should not be read as a randomized head-to-head comparison, and a population definition does not tell readers how many outcome measurements were available at every visit.

Finally, the terminated status and missing primary outcome estimates limit what can be inferred. Statistical interpretation depends not only on the design, but also on estimates, uncertainty, analysis choices, and completeness of follow-up. This record offers meaningful design and safety context, while leaving those central comparative questions unresolved.

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 efficacy is that the registry record does not report the primary endpoint results. It gives no group means, standard errors, between-group estimates, confidence intervals, or p-values for the pain ratings. The size, direction, and precision of the treatment comparisons therefore cannot be assessed.

The endpoint was planned at several time points, but the registry does not identify a single primary contrast or describe how repeated observations were analyzed. Multiplicity handling, model specification, and assumptions about correlation among repeated scores are not reported in the registry record. The record also does not describe missing-data methods or the number of observed scores at each visit.

Although the Full Analysis Population is defined, participant flow by group, withdrawals, treatment adherence, and the handling of post-discontinuation outcomes are not reported in the registry record. The record’s terminated status has no accompanying reason, so its implications for follow-up or analysis cannot be determined.

Safety summaries are limited to counts and listed serious-event terms. Definitions, event timing, exposure-adjusted summaries, and comparative statistical analyses are not reported. The open-label run-in safety group is separate in description from the double-blind groups, and the record does not explain its relationship to them. These limitations prevent a complete interpretation of efficacy and comparative safety from the registry record alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Efficacy of Buprenorphine Transdermal System (BTDS) in Subjects With Moderate to Severe Low Back Pain — NCT00313014.
• Registry record last updated 2012-09-03; status last verified 2012-08.
• Results first posted 2010-09-29.
• 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

NCT00313014 is recorded as a phase 3 randomized parallel-group trial in moderate to severe low back pain. It compared BTDS 20, BTDS 5, and oxycodone immediate-release, with a planned 12-week double-blind treatment period and supplemental acetaminophen or ibuprofen for all subjects. The primary measure was average pain over the last 24 hours at weeks 4, 8, and 12, on an 11-point scale from 0 to 10.

The record gives enrollment as 660 and defines the Full Analysis Population as randomized subjects who received at least one dose of double-blind study drug. It lists descriptive adverse-event counts for the double-blind groups and a separate open-label run-in period. The status is terminated; the reason is not reported in the registry record.

Primary outcome estimates and the statistical methods for efficacy, multiplicity, and missing data are not reported in the registry record. The available record therefore describes the study question and design but does not establish a comparative primary-outcome result.