Safety of Buprenorphine Transdermal Patch (BTDS) in Osteoarthritis Pain: a 52-Week Extension Phase: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety of Buprenorphine Transdermal Patch (BTDS) in Osteoarthritis Pain: a 52-Week Extension Phase (NCT01135524), a na phase 3 study. The primary outcome is The Number of Participants With Adverse Events as a Measure of Safety and Tolerability.

2. Clinical Question

The official title refers to a randomized, double-blind, active-comparator study, but the extension record describes a single-group phase and lists masking as none. The extension question should therefore be read as a safety follow-up question, not as a comparison of BTDS against an active control. The posted figures concern participants in the extension safety population; they do not establish what would have happened to those same participants under another treatment.

The brief summary describes starting qualified subjects on BTDS 5, with possible dose titration to BTDS 20. The registry record does not provide a separate treatment-effect estimate for pain control. Its stated focus is long-term safety and tolerability.

3. Trial Design

This is a Phase 3, single-group extension record for buprenorphine transdermal patch use in osteoarthritis pain. The registry lists enrollment as 196, allocation as NA, masking as none, and the study model as single group. The extension safety population is also reported as 196 participants, defined as people who received at least one dose of the open-label extension study drug and had at least one safety assessment.

The brief summary says qualified subjects began on BTDS 5 and could have their dose titrated, if necessary, to a maximum of BTDS 20 to achieve stable pain control. The listed intervention is buprenorphine transdermal patch. The official title mentions BTDS 20 or OxyIR versus BTDS 5, but the extension record's single-group design fields do not describe a concurrent randomized comparison among those options. The posted extension figures should not be read as evidence from a controlled contrast.

The planned safety observation period is described as 52 weeks. The record lists a start of 2004-04 and primary completion of 2005-08, and gives the study status as terminated. The reason for termination is not reported in the registry record. It also does not report the number of participants who completed the extension or their individual follow-up durations.

The registry lists one outcome measure and no analyses. The primary outcome is the number of participants with adverse events as a measure of safety and tolerability. Safety assessment is described as including adverse-event reports, clinical laboratory results, physical examination findings, and vital sign measurements. The available figures are limited to the posted adverse-event summaries; numerical results for the other assessment domains are not reported in the registry record.

Because there is no control group in the extension design, the record can describe the occurrence of reported safety events among participants who entered the safety population. It cannot separate treatment effects from the underlying condition, participants' other circumstances, or events that might also occur without BTDS exposure.

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: Subjects with moderate to severe osteoarthritis (OA) pain who required opioid analgesia; completed all visits of the double-blind phase on study drug, or who discontinued study drug due to lack of therapeutic effect in the double-blind phase and completed all visits of the double-blind phase off study drug were eligible for the extension phase.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Extension Safety Population (N = 196) consisted of all subjects who received at least 1 dose of the open-label BTDS extension study drug, and had at least 1 safety assessment during the extension phase.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as The Number of Participants With Adverse Events as a Measure of Safety and Tolerability, measured over 52 weeks.

The primary endpoint is titled the number of participants with adverse events, used as a measure of safety and tolerability over 52 weeks. Its unit is participants, and its parameter is a number rather than a mean or rate. The endpoint is therefore intended to count people who experienced an event, not to summarize the total number of event episodes or their severity in a single measure.

The record describes safety assessment through adverse-event reports, clinical laboratory results, physical examination findings, and vital sign measurements. These sources cover different aspects of safety: reported events capture experiences or diagnoses, while laboratory, examination, and vital-sign assessments can identify changes in measured health indicators. The registry record does not give numerical findings for those latter assessments.

Counting participants with events is useful for describing how many people were affected within the safety population. It does not, by itself, describe how often each person had events, how long events lasted, or whether an event was considered related to study treatment. Nor does a participant count establish a comparative risk when there is no concurrent control group. The posted record includes serious and other adverse-event figures, but does not provide an estimate of a treatment contrast or its precision.

The 52-week timeframe describes the endpoint's stated assessment period. Individual exposure and follow-up may differ, but those durations are not reported in the registry record. That distinction matters because a simple participant count does not adjust for variation in time at risk.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical information in the registry is sparse. It identifies a participant-count endpoint and posts adverse-event counts, but lists no analyses. The statistical interpretation is therefore principally descriptive. General explanations below clarify what the endpoint and common analytic choices mean; they do not imply that a particular unreported method was used in this trial.

What does a participant count represent?

A count of participants with an event reports how many people in the defined population experienced an event at least once. It differs from an event count, which can include repeated episodes in the same person. It also differs from an event rate, which relates event occurrence to time at risk. The primary endpoint is expressed in participants, and the record's adverse-event summary gives the number at risk and the number affected for serious and other events. No total episode count or person-time analysis is reported.

For this endpoint, the population definition is important. The Extension Safety Population consists of participants who received at least one dose and had at least one safety assessment. A participant who did not receive a dose or had no safety assessment would not meet that definition. The record does not describe how many people were screened, entered the extension but lacked an assessment, or stopped treatment before the planned timeframe.

Why does the single-group design matter?

In general, a concurrent comparator helps distinguish the outcomes observed under one treatment from outcomes that could arise under other conditions. Random allocation can make groups comparable on average, though it does not remove all uncertainty. Here, the registry lists allocation as NA and the study model as single group; masking is listed as none. There is no like-for-like control comparison in the posted extension data. As a result, the observed counts describe this group's experience and do not estimate a contrast between treatments.

The official title includes active-comparator and randomized language, but interpretation of the extension results must follow the extension record's design fields and the stated single-group model. The record does not provide an analysis connecting the extension counts to outcomes from an earlier or separate comparison.

How should uncertainty be understood?

In general, a point estimate is a single summary derived from observed data, while a confidence interval communicates uncertainty around that estimate under a specified model and sampling assumptions. For a participant count, a confidence interval would commonly be relevant to an estimated event proportion; for a treatment comparison, an interval would quantify uncertainty in the difference or ratio between groups. The registry record does not post confidence intervals, p-values, or a comparative effect estimate. No inferential conclusion about a treatment contrast can be drawn from the listed counts alone.

In general, an unadjusted re-calculation based on summary data can differ from a sponsor's analysis if the sponsor used a different population, model, or data handling. No sponsor analysis or recalculated comparison is listed in this record, so there is no such estimate to reconcile. The absence of a reported analysis should not be filled by assuming a particular model.

Why can time at risk matter?

In general, participants may have different exposure or follow-up durations. A simple count of people with at least one event does not account for those differences. Time-to-event methods or rates using person-time can address some timing questions, but require suitable data and assumptions. The registry states a 52-week timeframe but does not report individual follow-up times, event times, or a time-to-event analysis. The posted counts should therefore be read as participant counts, not as time-adjusted rates.

Over-dispersion is a general issue for count models when event counts vary more than a model expects. It can make standard errors from a simple count model too small if the model's variance assumptions do not fit the data. That concern is distinct from a participant-level indicator for whether any event occurred. The registry record does not report a count-model analysis or information needed to assess over-dispersion.

What do planning calculations mean?

In general, sample-size calculations depend on assumptions about the effect to detect, the significance level, allocation, and statistical method. A planning illustration based on an observed effect is not the same as the original trial's design justification, and it is not observed power. The record states assumptions for planning illustrations, including a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those assumptions do not turn this single-group extension into a two-arm comparison, nor do they establish that the trial was designed using those assumptions. Its sample-size justification is not reported in the registry record.

For a binary outcome, an illustration of participants per arm describes a hypothetical planning setup, not the number of participants actually analyzed in each arm of this extension. This distinction is particularly important when the observed record is single-group and has no randomized comparator. The registry does not report a statistical analysis plan, interim analyses, or the method used to handle missing outcome data.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one outcome measure and no analyses. It does not report a multiplicity strategy, such as a hierarchy for multiple outcomes or an adjustment for repeated statistical testing. Since no inferential analyses are posted, the record does not allow assessment of how multiplicity might have affected statistical conclusions. The absence of a reported strategy is not evidence that a particular adjustment was or was not used outside the registry entry.

The Extension Safety Population is defined as participants who received at least one dose of the open-label extension study drug and had at least one safety assessment. Its reported size is 196. This is a safety population definition, not necessarily an intention-to-treat definition. The registry does not provide a separate analysis population, describe exclusions, or give a participant flow that would show how people moved from enrollment into follow-up and analysis.

Missing-data handling is not reported in the registry record. There is no description of imputation, censoring, how incomplete safety assessments were treated, or how participants who stopped early contributed to the outcome summaries. The record also does not report individual exposure duration or completion status. These omissions limit assessment of whether all participants had comparable opportunity to experience and report events during the stated 52-week timeframe.

Because the endpoint is a count of participants with events, incomplete follow-up could affect whether an event was observed. In general, methods for handling missingness rely on assumptions about why data are missing and how missing participants differ from those observed. Those assumptions cannot be evaluated from the posted information. No conclusions about missingness or robustness to missing-data choices should be inferred.

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: aggravated osteoarthritis (0.5%), atypical chest pain (0.5%), cerebrovascular accident (0.5%), chest pain (0.5%), gangrene right foot (0.5%).

The serious-event summary reports 14 affected participants among 196 at risk in the extension phase. The other adverse-event summary reports 93 affected participants among 196 at risk. These figures count participants in the respective posted categories, not the total number of events. They do not indicate how many events an individual participant had or how long an event lasted.

The serious-event terms listed are aggravated osteoarthritis, atypical chest pain, cerebrovascular accident, chest pain, gangrene right foot, and gastroenteritis, each reported at 0.5%. The registry record does not give the event-level details needed to determine timing, seriousness criteria, relationship to treatment, or outcome. It also does not report a death count.

In general, event categories can overlap at the participant level: a person may experience events from more than one category or term. Thus category counts should not be added to estimate the number of unique participants unless the record explicitly establishes that categories are mutually exclusive. These summaries are descriptive of the observed extension safety population. Without a concurrent control group, they do not establish comparative risk or causation.

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

The posted results describe adverse events among participants in a 52-week, single-group BTDS extension. The record reports 14 participants affected by serious adverse events and 93 affected by other adverse events, each among 196 at risk. It also names serious adverse-event terms with a reported frequency of 0.5% each. These summaries convey that safety events were recorded in the extension population; they do not, by themselves, characterize each participant's clinical course or the total number of episodes.

The results do not show whether BTDS caused any specific event. The extension has no concurrent control group according to the registry design fields, so the posted counts cannot distinguish treatment-related events from events associated with osteoarthritis, other health conditions, background risk, or other circumstances. Nor do they estimate whether event frequency would differ under another treatment.

The results also do not establish the efficacy of BTDS for pain. Although the title and brief summary refer to pain and dose titration, the primary outcome is a safety and tolerability measure. No efficacy estimate is listed in the posted results. The record's numerical laboratory, physical examination, and vital sign findings are not reported, even though these are described as components of safety assessment.

In general, a registry outcome summary is limited by the outcome definitions, follow-up, population, and analyses recorded. Here, individual follow-up durations, missing-data methods, event timing, and event attribution are not reported. The status is terminated, but the reason is not reported in the registry record. These limits make the figures useful as descriptive counts, while leaving important questions about completeness, precision, and causality unanswered.

The findings therefore support a narrow reading: the registry records adverse events during the extension among participants meeting its safety-population definition. They do not support a causal claim, a comparative safety conclusion, or a conclusion about pain benefit.

13. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between describing safety events and estimating a treatment effect. The extension record contains participant counts in a defined safety population, but its design fields identify a single group rather than a concurrent randomized comparison. Descriptive safety reporting remains useful, yet it answers a different question from whether outcomes differ between treatments.

The endpoint's unit is participants. That choice makes the summary accessible as a count of people affected, but it does not capture repeated events, event duration, or time at risk. A reader should not mistake affected-participant counts for event totals or adjusted rates. Those distinctions are central when interpreting safety outcomes across follow-up periods.

The population definition also shapes the meaning of the results. Participants had to receive at least one dose and have at least one safety assessment to be included. Without a participant flow, follow-up details, or missing-data methods, the extent to which the summary represents everyone who entered the extension cannot be assessed from the registry record.

Finally, the contrast between the official title's active-comparator language and the extension record's single-group fields underscores the importance of identifying which study phase a result describes. Statistical interpretation depends on the design that generated the posted data, not on assuming that every element named in a broader title applies to the extension. The record supports a description of observed safety reports, but not a controlled comparison or causal 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 extension's single-group design is a central limitation for comparative interpretation. The registry lists allocation as NA, masking as none, and the model as single group. Although the official title names active-comparator and randomized features, the extension record does not provide a like-for-like control comparison. Consequently, the adverse-event counts cannot estimate relative safety against another treatment.

The record is marked terminated, but the reason for termination is not reported in the registry record. It does not state whether termination affected follow-up or outcome collection. The planned timeframe is 52 weeks, but actual exposure and follow-up durations, completion status, and participant flow are not reported. The number enrolled and the defined safety-population size are both listed as 196, but those figures do not substitute for a flow description.

Safety assessment is described broadly, including adverse-event reports, clinical laboratory results, physical examinations, and vital signs. Numerical results for the latter assessment types are not reported in the registry record. Event timing, duration, treatment attribution, and detailed outcome information are also absent. A death count is not reported.

The record lists no analyses, confidence intervals, p-values, or adjusted comparisons. It does not report a statistical analysis plan, multiplicity approach, sample-size justification, interim analyses, or missing-data methods. Without this information, the precision and robustness of the event summaries cannot be evaluated fully. The available counts remain descriptive, and their interpretation is limited to the safety population as defined in the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety of Buprenorphine Transdermal Patch (BTDS) in Osteoarthritis Pain: a 52-Week Extension Phase — NCT01135524.
• Registry record last updated 2012-09-10; status last verified 2012-09.
• Results first posted 2010-09-23.
• 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

NCT01135524 is a Phase 3 record titled Safety of Buprenorphine Transdermal Patch (BTDS) in Osteoarthritis Pain: a 52-Week Extension Phase. It lists Purdue Pharma LP as sponsor, enrollment of 196, a start of 2004-04, primary completion of 2005-08, and status terminated.

The extension is described as single group, with allocation NA and masking none. Qualified subjects began BTDS 5, with possible titration to a maximum of BTDS 20. The primary outcome concerns the number of participants with adverse events as a measure of safety and tolerability over 52 weeks.

The Extension Safety Population consists of 196 participants who received at least one dose and had at least one safety assessment. The registry posts serious adverse events for 14 participants and other adverse events for 93 participants. It lists no analyses. The reason for termination and additional details about follow-up, missing data, and event attribution are not reported in the registry record.