This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study of Breakthrough Cancer Pain: Assessment of Fentanyl Buccal Tablets Titration and Treatment in Opioid-Tolerant Patients (NCT00842829), a randomized phase 4 study. The primary outcome is Percentage of Participants Reaching an Effective Fentanyl Buccal Tablet (FBT) Dose As Assessed by the Participant During the Titration Period.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00842829 |
| Phase | Phase 4 |
| Condition | Cancer Pain, Breakthrough Pain |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | None (open label) |
| Enrollment | 330 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Cephalon |
| Results posted | Yes |
2. Clinical Question
Population
Opioid-tolerant patients with cancer pain and breakthrough pain. The primary analysis included participants who took at least one dose of study medication.
Intervention
Fentanyl buccal tablets, with titration starting at 100 mcg. The dose could be increased to a maximum of 800 mcg during a maximum titration timeframe of 7 days.
Comparator
Fentanyl buccal tablets, with titration starting at 200 mcg. The same maximum dose and titration timeframe are described for this group.
Primary question
What percentage of participants reached an effective fentanyl buccal tablet dose during titration, comparing the two starting-dose groups? The registry defines an effective dose using participant assessment across consecutive breakthrough-pain episodes.
The trial addressed the titration step rather than a comparison of fentanyl with no study treatment or with another drug. Both groups received fentanyl buccal tablets, but started at different doses. The primary outcome focused on whether participants reached an individually effective dose during the titration period, rather than on a single pain score or a comparison of long-term treatment outcomes.
The registry describes the study as pragmatic and multicenter, and identifies the population as opioid-tolerant patients with cancer. It does not report additional eligibility criteria in the record. Nor does the primary outcome by itself describe how quickly a participant reached an effective dose, how much pain relief was experienced across all episodes, or the balance of benefit and undesirable effects for each participant. Those are distinct questions, some of which appear among the secondary outcomes.
3. Trial Design
This was a phase 4, randomized, open-label, parallel-group study of fentanyl buccal tablet titration in patients with breakthrough cancer pain. The registry reports enrollment of 330. The study began in 2009-01, had primary completion in 2011-05, and is listed as terminated. The registry does not report why the study was terminated.
Participants were assigned to titration beginning at 100 mcg or 200 mcg. In either group, the dose could be increased until an effective dose was reached, with a maximum dose of 800 mcg and a maximum titration timeframe of 7 days. Participants who reached an effective dose could enter the open-label treatment period. The available arm descriptions are truncated, so further details of that period are not reported in the registry record.
Randomization can help balance measured and unmeasured participant characteristics across groups, while a parallel-group design assigns participants to one group rather than having each participant receive both starting doses. The registry does not report the randomization procedure, allocation concealment, or the planned allocation ratio. The study had no masking, meaning that it was open-label; the record does not specify how awareness of the starting dose was considered in participant-reported assessments.
The primary analysis population was the titration safety analysis set: participants who took at least one dose of study medication. It included 145 participants in the 100 mcg group and 167 in the 200 mcg group. These analysis counts are not the same as the registry's overall enrollment figure; the reasons for the difference are not reported in the registry record. The primary outcome was assessed during Day 1 up to Day 7. Secondary outcomes included time to meaningful pain relief, reaching an effective dose, use of rescue medication, medication performance, and several Brief Pain Inventory subscales.
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.
Dose Titration Period
| Stage | FBT 100 Mcg - Dose Titration Period | FBT 200 Mcg - Dose Titration Period | FBT - Treatment and Continuation Periods |
|---|---|---|---|
| STARTED | 156 | 174 | 0 |
| Titration Safety Analysis Set | 145 | 167 | 0 |
| COMPLETED | 130 | 151 | 0 |
| NOT COMPLETED | 26 | 23 | 0 |
Reasons for not completing this period:
| Reason | FBT 100 Mcg - Dose Titration Period | FBT 200 Mcg - Dose Titration Period | FBT - Treatment and Continuation Periods |
|---|---|---|---|
| Adverse Event | 11 | 10 | 0 |
| Lack of Efficacy | 4 | 1 | 0 |
| Unstable persistent cancer pain | 1 | 0 | 0 |
| Withdrawal by Subject | 2 | 6 | 0 |
| Other | 5 | 4 | 0 |
| Non-compliance to study procedures | 1 | 1 | 0 |
| Non-compliance to study drug | 2 | 1 | 0 |
Treatment Period
| Stage | FBT 100 Mcg - Dose Titration Period | FBT 200 Mcg - Dose Titration Period | FBT - Treatment and Continuation Periods |
|---|---|---|---|
| STARTED | 0 | 0 | 281 |
| Safety Analysis Set | 0 | 0 | 223 |
| COMPLETED | 0 | 0 | 218 |
| NOT COMPLETED | 0 | 0 | 63 |
Reasons for not completing this period:
| Reason | FBT 100 Mcg - Dose Titration Period | FBT 200 Mcg - Dose Titration Period | FBT - Treatment and Continuation Periods |
|---|---|---|---|
| Adverse Event | 0 | 0 | 15 |
| Lack of Efficacy | 0 | 0 | 6 |
| Unstable persistent cancer pain | 0 | 0 | 5 |
| Withdrawal by Subject | 0 | 0 | 11 |
| Consistently >4 BTP episodes daily | 0 | 0 | 1 |
| Protocol Violation | 0 | 0 | 2 |
| Other | 0 | 0 | 18 |
| Non-compliance to study procedures | 0 | 0 | 4 |
| Unclear completion status | 0 | 0 | 1 |
Continuation Period
| Stage | FBT 100 Mcg - Dose Titration Period | FBT 200 Mcg - Dose Titration Period | FBT - Treatment and Continuation Periods |
|---|---|---|---|
| STARTED | 0 | 0 | 88 |
| Continuation Safety Analysis Set | 0 | 0 | 87 |
| COMPLETED | 0 | 0 | 27 |
| NOT COMPLETED | 0 | 0 | 61 |
Reasons for not completing this period:
| Reason | FBT 100 Mcg - Dose Titration Period | FBT 200 Mcg - Dose Titration Period | FBT - Treatment and Continuation Periods |
|---|---|---|---|
| Adverse Event | 0 | 0 | 32 |
| Lack of Efficacy | 0 | 0 | 6 |
| Unstable persistent cancer pain | 0 | 0 | 3 |
| Withdrawal by Subject | 0 | 0 | 10 |
| Other | 0 | 0 | 7 |
| Non-compliance to study procedures | 0 | 0 | 2 |
| Non-compliance to study drug | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Titration safety analysis set consisting of participants who took at least one dose of study medication.
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.
| Characteristic | Unit | FBT 100 Mcg - Dose Titration Period | FBT 200 Mcg - Dose Titration Period | Total |
|---|---|---|---|---|
| Participants analysed | 156 | 174 | 330 | |
| Age Continuous | years | 59.5 (SD 11.72) | 60.1 (SD 10.97) | 59.8 (SD 11.32) |
| Sex: Female, Male: Female | Participants | 71 | 78 | 149 |
| Sex: Female, Male: Male | Participants | 85 | 96 | 181 |
| Region of Enrollment: France | participants | 16 | 25 | 41 |
| Region of Enrollment: Spain | participants | 26 | 26 | 52 |
| Region of Enrollment: Poland | participants | 38 | 41 | 79 |
| Region of Enrollment: Ireland | participants | 1 | 0 | 1 |
| Region of Enrollment: Germany | participants | 32 | 38 | 70 |
| Region of Enrollment: United Kingdom | participants | 8 | 7 | 15 |
| Region of Enrollment: Italy | participants | 35 | 37 | 72 |
| Cancer Site: Breast | participants | 31 | 36 | 67 |
| Cancer Site: Colon/rectum | participants | 15 | 25 | 40 |
| Cancer Site: Colon/rectum + Pancreas/stomach + other | participants | 1 | 0 | 1 |
| Cancer Site: Head/neck | participants | 12 | 12 | 24 |
| Cancer Site: Leukemia/lymphoma | participants | 2 | 4 | 6 |
| Cancer Site: Myeloma | participants | 5 | 4 | 9 |
| Cancer Site: Oesophageal | participants | 4 | 2 | 6 |
| Cancer Site: Pancreas/stomach | participants | 13 | 11 | 24 |
| Cancer Site: Prostate | participants | 8 | 17 | 25 |
| Cancer Site: Lung | participants | 26 | 21 | 47 |
6. Primary Endpoint
The registry lists the primary outcome as Percentage of Participants Reaching an Effective Fentanyl Buccal Tablet (FBT) Dose As Assessed by the Participant During the Titration Period, measured over Day 1 up to Day 7.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | percentage of treated participants |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was the percentage of participants who reached an effective fentanyl buccal tablet dose, as assessed by the participant during the titration period. The assessment covered Day 1 up to Day 7 and was recorded in the titration-period diary. The analysis population consisted of participants who took at least one dose of study medication.
The registry defines an effective dose as one that provided adequate analgesia within the first 30 minutes after study drug administration and minimized undesirable effects for 2 consecutive breakthrough-pain episodes. The next episode was used to confirm the dose; if confirmed, the participant used that dose for following episodes. This definition makes the endpoint a participant-level measure of reaching a dose that met the stated relief and tolerability criteria, rather than a measure of average pain intensity alone.
This endpoint is relevant to a titration comparison because the study aim concerned the proportion reaching an effective dose after starting at either dose. It does not, by itself, indicate how long titration took for each participant, the magnitude of pain relief, or whether the dose remained suitable over a longer period. Time to meaningful relief and other patient-reported outcomes were listed as secondary outcomes. Arm-level primary outcome values were 75.2 for 145 participants in the 100 mcg group and 81.2 for 167 participants in the 200 mcg group. The registry does not attach confidence intervals to these arm-level percentages.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary outcome values are 75.2 for the 100 mcg starting-dose group and 81.2 for the 200 mcg starting-dose group. These percentages describe participants in the titration safety analysis set who reached an effective dose under the registry's participant-assessed definition. They should be read as observed results in the analyzed groups, not as guarantees about the experience of an individual participant.
The registry also reports a net mean difference of -6.3 for the two groups and identifies the analysis as noninferiority or equivalence. It gives a 95% confidence interval with an upper bound of 1.4, but does not report the lower bound or a p-value. The record does not explain the sign convention for the contrast. Therefore, the reported contrast cannot be translated confidently into a direction-specific statement about which group had the larger percentage using the contrast alone. The arm-level values are separately reported, but the registry does not provide confidence intervals around them.
A confidence interval expresses uncertainty about an estimated contrast under the assumptions of the analysis. A complete interval is needed to assess the range of values compatible with that estimate. For a noninferiority or equivalence assessment, interpretation also depends on a prespecified margin and the direction in which the contrast is defined. Neither the margin nor the full interval is reported in the registry record. The result therefore cannot be independently classified as establishing noninferiority or equivalence from the available information.
The endpoint is a composite participant judgment in the sense that adequate analgesia and minimized undesirable effects both figure in the definition. The registry does not report separate primary results for relief and undesirable effects, so the overall percentages do not show which part of the definition most often determined whether a dose was considered effective. The study was open-label and relied on participant assessment, which is important context when interpreting a subjective endpoint.
The registry lists other outcomes, including time to meaningful pain relief, rescue medication use, medication performance, and changes in Brief Pain Inventory subscales. Their presence broadens the clinical questions considered, but the primary contrast should not be treated as a complete summary of all these outcomes. The record lists 23 secondary outcomes as posted, but does not report a multiplicity adjustment or a complete account of how results across outcomes were interpreted.
These results describe the trial's posted outcome and analysis, not proof of a general treatment effect. The information available does not establish how the groups compared on every aspect of pain relief, tolerability, safety, or longer-term outcomes. It also does not support a recommendation about which starting dose should be used in clinical care.
9. Statistical Methods Explained
The primary outcome is a percentage: the proportion of participants in each titration group who reached an effective dose as assessed by the participant. The registry reports the group values and an analysis classified as noninferiority or equivalence. It does not report the analysis method, the hypothesis details, or a noninferiority or equivalence margin. The interpretation must therefore distinguish the observed percentages from the formal analysis of the contrast.
What does the percentage measure?
A participant contributes to the endpoint by meeting the registry's criteria during the titration period. Those criteria require adequate analgesia within the first 30 minutes and minimized undesirable effects for 2 consecutive breakthrough-pain episodes, followed by confirmation at the next episode. The endpoint is thus a proportion of participants who reached the specified state, not a count of pain episodes and not an average pain score. The registry reports 75.2 for the group starting at 100 mcg and 81.2 for the group starting at 200 mcg.
The primary population is the titration safety analysis set, defined as participants who took at least one dose of study medication. The analysis counts were 145 and 167, respectively. Restricting analysis to treated participants is distinct from analyzing every randomized participant regardless of treatment received. Whether a different analysis population was prespecified or used is not reported in the registry record.
How should the contrast be read?
The registry reports a net mean difference of -6.3 with a 95% confidence interval whose upper bound is 1.4. It does not give the lower bound or a p-value, and it does not describe the sign convention. Since the group percentages are available but the contrast's direction is not explained, the contrast should be quoted as reported rather than assigned a direction that the record does not establish.
In general, a confidence interval gives a range of estimates compatible with the observed data and the assumptions used in the analysis. Its width conveys precision: a narrower interval indicates less statistical uncertainty than a wider one, all else equal. A 95% confidence interval is not a statement that a particular participant's outcome has a 95% chance of falling within the interval. Here, the incomplete interval limits assessment of the estimate's precision and prevents a reader from checking the full range against a clinical or statistical threshold.
What does noninferiority or equivalence require?
In general, a noninferiority analysis asks whether the data rule out a disadvantage larger than a prespecified margin. An equivalence analysis asks whether the uncertainty interval lies within prespecified limits on both sides. The margin and interval are central to these interpretations; a point estimate alone is not enough. The registry labels the analysis as noninferiority or equivalence, but the margin, detailed hypothesis, and complete interval are not reported. No conclusion about meeting such a criterion can be reconstructed from the available record.
Why does the open-label design matter?
Random assignment is intended to make comparisons between groups less vulnerable to systematic differences in who receives each starting dose. The registry identifies randomization, but does not report the generation or concealment methods. Participants and investigators were not masked. Since the endpoint depended on participant assessment and diary reporting, awareness of the starting dose could potentially influence assessment or reporting in general. That is a methodological consideration, not evidence that such influence occurred in this trial. The registry does not report a procedure to assess or correct for it.
The registry lists one analysis and 24 outcome measures, including the primary outcome and secondary outcomes. It does not describe a multiplicity strategy. When many outcomes are assessed, the chance of at least one apparently unusual result can increase if results are interpreted without accounting for the number of comparisons. This general concern does not change the primary endpoint's definition, but it matters when reading secondary findings. The record does not state whether analyses were prespecified in a protocol or statistical analysis plan.
What can planning calculations tell readers?
Sample-size illustrations based on an observed effect are planning exercises, not observed trial results and not observed power. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The illustration convention uses total events for time-to-event outcomes and participants per arm for other outcomes. Numerical planning estimates are not reported in the registry record, and these assumptions are not a substitute for the trial's own design justification. The registry does not report the trial's sample-size justification.
General statistical concepts can help frame the result, but they do not fill in missing analytic details. In particular, the endpoint's analysis model, handling of missing data, full contrast interval, margin, and multiplicity approach are not reported in the registry record. These omissions constrain how far the posted result can be interpreted independently.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| not stated | Mean Difference (Net) -6.3 | not reported | not reported |
The registry posts a sponsor analysis classified as noninferiority or equivalence, reporting a net mean difference of -6.3 and a 95% confidence interval with an upper bound of 1.4. A lower bound, p-value, detailed method, and noninferiority or equivalence margin are not reported in the registry record. The sponsor's result is therefore the available formal comparison, but the information needed to evaluate its criterion fully is incomplete.
No separate recalculated contrast or confidence interval is reported in the registry record. The posted arm-level percentages, 75.2 in the 100 mcg group and 81.2 in the 200 mcg group, are descriptive results and should not be substituted for the sponsor's inferential analysis. The registry does not flag a discrepancy between the sponsor result and a recalculation. Without a separately reported recalculation, there is no independent numerical estimate to compare with the sponsor analysis.
In general, a recalculation from summary statistics would be unadjusted and could differ from a sponsor analysis that used a specified model or analysis population. Such a recalculation would not override the trial's own analysis. In this record, the sponsor's reported analysis remains the only posted formal contrast, while its interpretation is limited by the missing details.
11. Multiplicity, Missing Data and Analysis Populations
The registry lists 24 outcome measures and 23 secondary outcomes as posted, and reports one analysis. The primary outcome is the percentage reaching an effective dose during titration. Secondary outcomes include time to meaningful pain relief, the number reaching an effective dose, rescue medication use, medication performance, and changes in Brief Pain Inventory subscales related to general activity, mood, walking ability, and normal work.
Assessing multiple outcomes raises a general multiplicity issue: if many statistical comparisons are examined, some results may appear notable by chance. A multiplicity adjustment can change the error rate used for interpretation, but the registry does not report whether any adjustment was planned or applied. Nor does it report which outcomes were designated as confirmatory beyond identifying the primary outcome. No p-value is posted for the primary comparison, and the registry does not provide a full account of statistical testing across outcomes.
Information about missing data and analysis populations is also limited. The primary population is defined as participants who took at least one dose of study medication, with 145 participants in the 100 mcg group and 167 in the 200 mcg group. The record does not explain missing outcome handling, whether participants without an assessable endpoint were excluded, or how withdrawals were handled. The reasons that the analysis counts differ from the overall enrollment of 330 are not reported in the registry record.
The registry's skip note says values were missing or not estimable for a two-arm comparison for a count-other endpoint. It does not identify a missing-data method that could address such unavailable outcomes. Details such as imputation, sensitivity analyses, or assumptions about unobserved outcomes are not reported in the registry record. These gaps matter because complete-case results can differ from results under other missing-data assumptions, particularly when outcome availability is related to participant experience or treatment assignment. The record does not establish whether that concern affected this trial.
12. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| FBT - All Doses and Study Periods | 67 | 312 | 21.5% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| FBT - All Doses and Study Periods | 52 of 312 |
Most frequent serious adverse event terms
| Event term | Organ system | FBT - All Doses and Study Periods |
|---|---|---|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 21 of 312 |
| Renal failure | Renal and urinary disorders | 5 of 312 |
| Vomiting | Gastrointestinal disorders | 4 of 312 |
| Anaemia | Blood and lymphatic system disorders | 3 of 312 |
| Pyrexia | General disorders | 3 of 312 |
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | 3 of 312 |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | 3 of 312 |
| Cardio-respiratory arrest | Cardiac disorders | 2 of 312 |
| Dysphagia | Gastrointestinal disorders | 2 of 312 |
| Intestinal obstruction | Gastrointestinal disorders | 2 of 312 |
Most frequent non-serious adverse event terms
| Event term | Organ system | FBT - All Doses and Study Periods |
|---|---|---|
| Nausea | Gastrointestinal disorders | 30 of 312 |
| Vomiting | Gastrointestinal disorders | 23 of 312 |
| Somnolence | Nervous system disorders | 16 of 312 |
Serious events with the highest arm-level rate: malignant neoplasm progression (6.7%), renal failure (1.6%), vomiting (1.3%), anaemia (1.0%), pyrexia (1.0%).
Safety results are reported for a pooled group receiving fentanyl buccal tablets across all doses and study periods, rather than separately for the two starting-dose groups. Among 312 participants at risk, 67 were reported as affected by serious adverse events. For other adverse events, 52 of 312 participants were reported as affected. These counts describe the safety group as posted and do not show comparative risk by starting dose.
The registry lists the most frequent serious adverse event terms with percentages: malignant neoplasm progression, 6.7%; renal failure, 1.6%; vomiting, 1.3%; anaemia, 1.0%; pyrexia, 1.0%; and respiratory failure, 1.0%. These are registry-listed terms and percentages. The record does not provide a starting-dose breakdown for these terms or details sufficient to determine whether each percentage refers to participants, events, or another reporting basis.
Deaths are not reported in the registry record. The pooled presentation and the absence of an arm-level comparison mean these figures cannot establish whether serious adverse events differed between the starting-dose groups. They also do not by themselves establish causation. Safety figures should be read alongside the stated population and period of observation, while recognizing that further details about event definitions and collection are not reported in the registry record.
13. What the Result Does, and Does Not, Mean
The primary outcome describes how often participants in each starting-dose group reached a dose that met the registry's participant-assessed criteria during titration. The posted values are 75.2 for the group starting at 100 mcg and 81.2 for the group starting at 200 mcg. These results address a specific titration question over Day 1 up to Day 7. They do not summarize every aspect of pain relief or treatment experience.
The result does not show that one starting dose is preferable for every participant. Participants were assessed individually, and the endpoint incorporated both adequate analgesia and minimized undesirable effects. A group percentage cannot describe the range of individual responses, the dose ultimately reached by each participant, or how many episodes were needed for each person. The record does not provide those individual-level results.
The posted analysis is identified as noninferiority or equivalence, but its margin and complete confidence interval are not reported. As a result, the registry information does not allow a reader to verify whether a prespecified noninferiority or equivalence criterion was met. The reported arm percentages and the sponsor's incomplete contrast should not be treated as interchangeable evidence.
The endpoint also does not establish longer-term outcomes. Although secondary measures included treatment-period outcomes and Brief Pain Inventory subscales, the primary endpoint was confined to titration. The record does not support conclusions about longer-term pain control, quality of life, or the comparative safety of the two starting doses. Safety results are pooled across doses and study periods, so they do not provide a dose-group comparison.
More broadly, a registry result is evidence about the participants and analyses recorded for this study. It is not medical advice and does not determine an appropriate treatment choice for an individual. The trial was open-label, and its primary outcome depended on participant assessment; this context should be considered alongside the randomized design. Missing details about the analysis plan, missing outcomes, and the incomplete inferential result limit the strength of conclusions that can be drawn from the registry record alone.
14. Why This Trial Matters Statistically
This trial poses a statistical question that is common in dose titration: whether different starting doses are associated with different proportions of participants reaching an individually effective dose within a defined period. The outcome is more complex than a simple dose attainment measure because its definition includes both adequate analgesia and minimized undesirable effects, based on participant reports across consecutive breakthrough-pain episodes.
The randomized parallel-group design provides a framework for comparing the two starting-dose strategies. At the same time, the open-label design and participant-assessed primary outcome make careful interpretation important. Randomization supports comparison, but it does not remove all measurement concerns or replace a complete account of the analysis method. The registry identifies the study design but leaves several methodological details unreported.
The case also illustrates why the label noninferiority or equivalence is not enough to interpret a result. The margin and full confidence interval are needed to judge whether the data satisfy the chosen criterion. Here, the record supplies only an upper confidence bound, so the formal claim cannot be evaluated completely from the posted information.
Finally, the titration endpoint and pooled safety reporting answer different questions. The primary result concerns reaching a participant-assessed effective dose, while the safety figures aggregate participants across all doses and periods. Keeping those questions separate prevents a titration percentage from being mistaken for a comprehensive benefit-risk comparison. The registry's missing-data and multiplicity details also show why statistical transparency matters when several outcomes are recorded.
15. 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 registry record leaves important details about the primary comparison unreported. It does not give the full 95% confidence interval, a p-value, the analysis method, or the noninferiority or equivalence margin. Without the margin and complete interval, the sponsor's analysis cannot be independently checked against its stated classification. The sign convention for the reported contrast is also not explained.
The design is described as randomized and open-label, but the randomization procedure and allocation concealment are not reported. Because the primary endpoint relied on participant assessment and a diary, lack of masking is relevant context. The record does not describe procedures for minimizing or evaluating possible reporting effects.
The primary analysis included participants who took at least one study dose, and the reasons for the difference between this population and overall enrollment are not reported. Handling of missing outcome data, withdrawals, and any sensitivity analyses is not reported in the registry record. The record also does not state whether multiplicity was addressed across the 24 outcome measures.
Safety results are pooled across doses and study periods, so they do not permit a direct safety comparison between starting-dose groups. The arm descriptions are truncated, limiting the available detail about the open-label treatment period. The registry lists the study as terminated but does not report the reason. These limitations do not invalidate the posted observations, but they narrow the conclusions that can be drawn from them.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: Study of Breakthrough Cancer Pain: Assessment of Fentanyl Buccal Tablets Titration and Treatment in Opioid-Tolerant Patients — NCT00842829.
- Registry record last updated 2012-10-01; status last verified 2012-09.
- Results first posted 2012-09-20.
- 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.
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19. Record Summary
NCT00842829 is a phase 4, randomized, open-label, parallel-group study of fentanyl buccal tablet titration for breakthrough cancer pain in opioid-tolerant patients with cancer. Participants started titration at 100 mcg or 200 mcg, with a maximum dose of 800 mcg and a maximum titration timeframe of 7 days. The registry reports enrollment of 330 and lists the study as terminated.
The primary endpoint was the percentage of participants reaching an effective dose during titration, assessed by the participant using criteria for adequate analgesia and minimized undesirable effects. The posted values were 75.2 among 145 participants in the 100 mcg group and 81.2 among 167 participants in the 200 mcg group. The registry also reports a net mean difference of -6.3 and an incomplete 95% confidence interval, with an upper bound of 1.4. The margin and full analysis details are not reported in the registry record.
Safety figures are pooled across doses and study periods. Missing-data methods, multiplicity handling, and the reason for termination are not reported in the registry record.