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 A Clinical Trial With Intranasal Fentanyl in Cancer Patients With Breakthrough Pain (NCT01429051), a na phase 3 study. The primary outcome is Induction Phase: Pain Intensity Difference at 10 Minutes (PID10) After Treatment.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01429051 |
| Phase | Phase 3 |
| Condition | Break Through Pain, Cancer |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | Double |
| Enrollment | 46 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Takeda |
| Results posted | Yes |
2. Clinical Question
Population
Cancer patients experiencing breakthrough pain. The registry record lists 46 enrolled participants. The primary analysis population was narrower: participants randomly assigned who entered the Efficacy Phase and received double-blind intranasal fentanyl for at least 1 breakthrough pain episode.
Intervention
Intranasal fentanyl spray, titrated step-wise to an effective dose of 50, 100, 200 or 400 μg. The stated primary efficacy question focuses on the 400 μg dose strength.
Comparator
Placebo is named as an intervention. The arm description says that participants titrated to 200 or 400 μg entered an 8-spray sequence in the Efficacy Phase, where breakthrough pain episodes were treated with study drug. The registry record also classifies the study as single-group with allocation listed as not applicable, so it does not establish a conventional parallel-group comparison.
Primary question
What was the pain intensity difference 10 minutes after the first dose during an episode of breakthrough pain? The outcome description defines a positive difference as reduced pain from baseline. The numerical estimate and its confidence interval are not reported in the registry record.
The clinical question combines a dose-titration process with a placebo-controlled, double-blind, randomised, cross-over phase, as described in the official title. That description suggests an effort to evaluate changes in pain within the treatment episodes and to compare study treatments under masking. However, the registry’s design fields identify a single-group model and no applicable allocation, and the record explicitly cautions that the arms are not a like-for-like control comparison. Those details make it important not to interpret the study as a standard randomized parallel-group trial.
The stated objective also includes safety and long-term nasal tolerability across dose strengths from 50 μg to 400 μg. Those objectives are distinct from the primary short-term pain endpoint. The record lists adverse event outcomes and nasal mucosa outcomes, but it does not report the results for the primary pain endpoint. Consequently, the posted information identifies the question the study was intended to address without allowing an estimate of the size or precision of the answer.
3. Trial Design
This was a Phase 3 clinical trial sponsored by Takeda and marked completed in the registry. The record lists 46 participants enrolled. Its title describes dose titration followed by a placebo-controlled, double-blind, randomised, cross-over efficacy phase, alongside a 12-week safety and nasal tolerability evaluation. The registry’s structured design fields, however, classify the study as single-group and list allocation as not applicable. The record cautions that this is not a randomized comparison and that the arms are not a like-for-like control comparison. These descriptions should be read together rather than treating the structured fields as evidence of a conventional parallel-arm trial.
In the Titration Phase, participants were step-wise titrated to an effective intranasal fentanyl dose of 50, 100, 200 or 400 μg. The arm description says participants titrated to 200 or 400 μg were randomized to an 8-spray sequence in the Efficacy Phase; it also states that 6 breakthrough pain episodes were treated with 400 μg intranasal fentanyl. The available arm description is incomplete, so it does not fully explain the sequence, treatment allocation, or the handling of the placebo episodes. Further protocol details are not reported in the registry record.
The registry lists three phases in its safety data: Titration, Efficacy and Tolerability. The posted counts differ by phase, and participants at risk were not the same in each phase. The record gives no further explanation of how participants entered or completed each phase. Thus, the phases should not be treated as independent parallel groups or as directly comparable cohorts without additional information.
The primary outcome is described as pain intensity difference at 10 minutes after treatment, with pain assessed at baseline and 10 minutes during efficacy episodes. The primary outcome title calls this the “Induction Phase,” while the timeframe and description refer to the Efficacy Phase. This terminology is not reconciled in the registry record. The registry also does not report the sample-size justification, detailed statistical plan, interim analyses, or full protocol-level design details.
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: The first dose of Intranasal Fentanyl Spray (INFS) was taken at the clinic for training purposes and was not related to treatment of a BTP episode. One patient received the initial 50 μg test dose but did not receive INFS for titration, but is included in the safety analysis set.
Titration Phase
| Stage | Intranasal Fentanyl Spray (INFS) |
|---|---|
| STARTED | 45 |
| COMPLETED | 33 |
| NOT COMPLETED | 12 |
Reasons for not completing this period:
| Reason | Intranasal Fentanyl Spray (INFS) |
|---|---|
| Death | 1 |
| Withdrawal by Subject | 7 |
| Physician Decision | 1 |
| Unsuccessful titration at any dose | 1 |
| Less than 3 BTP episodes per week | 2 |
Efficacy Phase
| Stage | Intranasal Fentanyl Spray (INFS) |
|---|---|
| STARTED | 15 |
| COMPLETED | 13 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | Intranasal Fentanyl Spray (INFS) |
|---|---|
| Adverse Event | 1 |
| Death | 1 |
Tolerability Phase
| Stage | Intranasal Fentanyl Spray (INFS) |
|---|---|
| STARTED | 31 |
| COMPLETED | 16 |
| NOT COMPLETED | 15 |
Reasons for not completing this period:
| Reason | Intranasal Fentanyl Spray (INFS) |
|---|---|
| Death | 5 |
| Adverse Event | 2 |
| Withdrawal by Subject | 5 |
| Physician Decision | 1 |
| Other | 2 |
Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set consisted of all randomly assigned participants who entered the Efficacy Phase (II) of the trial and were treated for at least 1 BTP episode with double-blind INFS in the Efficacy Phase of the trial.
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.
Population: The safety analysis set included all participants who received at least 1 dose of INFS (including the initial test dose).
| Characteristic | Unit | Intranasal Fentanyl Spray (INFS) |
|---|---|---|
| Participants analysed | 46 | |
| Age, Continuous | years | 61.0 (SD 9.09) |
| Sex: Female, Male: Female | Participants | 31 |
| Sex: Female, Male: Male | Participants | 15 |
| Race/Ethnicity, Customized: White | participants | 46 |
| Region of Enrollment: Hungary | participants | 33 |
| Region of Enrollment: Norway | participants | 10 |
| Region of Enrollment: Russian Federation | participants | 3 |
| Site of Primary Tumour Reported in >5% Patients: Breast | participants | 14 |
| Site of Primary Tumour Reported in >5% Patients: Lung respiratory system | participants | 5 |
| Site of Primary Tumour Reported in >5% Patients: Gastro-oesophageal | participants | 1 |
| Site of Primary Tumour Reported in >5% Patients: Colon/rectal | participants | 3 |
| Site of Primary Tumour Reported in >5% Patients: Pancreas | participants | 6 |
| Site of Primary Tumour Reported in >5% Patients: Female genital | participants | 3 |
| Site of Primary Tumour Reported in >5% Patients: Prostate | participants | 3 |
| Site of Primary Tumour Reported in >5% Patients: Urological | participants | 7 |
| Site of Primary Tumour Reported in >5% Patients: Unknown Primary Tumour | participants | 2 |
| Site of Primary Tumour Reported in >5% Patients: Liver | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Induction Phase: Pain Intensity Difference at 10 Minutes (PID10) After Treatment, measured over During the efficacy phase (II), at each episode of breakthrough pain, at 0 and 10 minutes after first dose of study drug..
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is Pain Intensity Difference at 10 Minutes, abbreviated in the record as PID10. Participants rated pain intensity during each breakthrough pain episode at baseline and 10 minutes after the first dose of study drug. The rating used an 11-point Numerical Rating Scale from 0 to 10, where 0 means absence of pain and 10 means worst possible pain. PID10 is the difference between the baseline and 10-minute pain ratings. A positive value represents a decrease in pain, and the record states that a reduction of at least 2 points is considered clinically important.
This endpoint is used to capture short-term change after treatment of an individual breakthrough pain episode. It focuses on the timing and symptom that the trial intended to evaluate rather than on a long-term average alone. Repeated episode assessments can characterize how pain changes across treated episodes, although the registry record does not describe the statistical handling of repeated observations or the relationship between episode-level measurements and participant-level summaries.
The outcome is reported as a least-squares mean with a 95% confidence interval. In general, a least-squares mean is an estimate derived from a statistical model and can account for model terms or structure; the exact model used for this endpoint is not reported in the registry record. A confidence interval expresses uncertainty around an estimate under the assumptions of the analysis. Here, neither the numerical least-squares mean nor its interval is reported, so the endpoint definition can be interpreted but its observed result cannot.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record defines a clinically interpretable primary outcome: the change in pain intensity from baseline to 10 minutes after the first dose during a breakthrough pain episode. Positive values represent improvement in the pain rating, and a reduction of at least 2 points is described as clinically important. These definitions explain the direction and scale of the endpoint, but they do not establish what the trial observed. The numerical primary estimate, its 95% confidence interval, and a primary-result p-value are not reported in the registry record.
Without those results, it is not possible to describe the magnitude of the observed change, assess how precisely it was estimated, or determine whether the estimate was near or far from the stated 2-point clinical-importance criterion. It is also not possible to assess whether the interval includes values representing no change or clinically important change. Any claim about the efficacy of the 400 μg dose based on the primary endpoint would therefore go beyond the posted results.
The trial’s design description warrants particular care. The official title describes a placebo-controlled, double-blind, randomised, cross-over phase, and the arm description refers to randomization to an 8-spray sequence for some titrated participants. In contrast, the structured design fields list a single-group model and allocation as not applicable. The registry explicitly cautions that this is not a randomized comparison and that arms are not a like-for-like control comparison. Accordingly, the record does not support a simple treatment-versus-control interpretation from the design fields or from the safety counts.
The registry describes a Full Analysis Set comprising randomly assigned participants who entered the Efficacy Phase and were treated for at least 1 breakthrough pain episode with double-blind intranasal fentanyl. This definition helps identify the intended analysis population, but the number of participants in that set and the primary analysis results are not reported in the registry record. The total enrollment of 46 should not be assumed to equal the analysis population for the primary endpoint.
The safety entries are presented by phase, with different numbers at risk in the Titration, Efficacy and Tolerability Phases. They describe events recorded in each phase, not a controlled comparison of treatment effects. The registry reports serious-event counts and other adverse-event counts, and it lists selected serious-event terms with percentages. The denominators underlying those term percentages are not specified in the posted record, and the phase groups differ in size. The entries therefore describe reported safety events but do not by themselves establish comparative risk.
Overall, the posted record gives useful definitions of the intended pain outcome, the titration doses, and the trial phases. It does not provide the primary numerical result needed to judge the observed effect or its uncertainty. The distinction between the stated design narrative and the structured design classification, as well as the phase-specific safety denominators, further limits direct comparative interpretation.
9. Statistical Methods Explained
What does the primary estimate represent?
The primary outcome is a continuous measure: pain intensity difference between baseline and 10 minutes after the first dose. A positive difference means that the pain rating decreased. The record specifies a least-squares mean as the summary measure. In general, a mean describes the central value of a continuous outcome, while a least-squares mean is typically estimated from a statistical model rather than calculated only as a raw arithmetic average. Such a model can account for features of the analysis, but the model terms and assumptions used for this endpoint are not reported in the registry record.
The outcome is assessed for breakthrough pain episodes, while the analysis population is defined at the participant level. When participants contribute repeated episodes, observations from the same participant may be related. General statistical methods for repeated measurements account for this dependence rather than treating every episode as fully independent. The registry record does not state which method was used, how many episode assessments contributed, or how incomplete episode records were handled.
How should the confidence interval be read?
The primary outcome is specified with a 95% confidence interval. In general, a confidence interval gives a range of estimates compatible with the observed data and the statistical model’s assumptions, and it conveys uncertainty in the estimate. A narrower interval indicates greater precision than a wider interval, all else being equal. It does not mean that there is a 95% probability that a particular fixed treatment effect lies within the calculated interval. The numerical interval for PID10 is not reported in the registry record, so its width and position cannot be assessed.
The clinical-importance reference is a reduction of at least 2 points on the 11-point scale. In general, comparing an estimate and its interval with a clinically meaningful threshold can help distinguish the direction and precision of a result from its clinical importance. That assessment requires the actual estimate and interval; the threshold alone is not evidence that the observed result reached it.
What is distinctive about the design?
In general, a cross-over design compares treatments within the same participant across treatment periods or episodes, which can reduce the influence of stable differences between participants. It also requires attention to sequence, period effects, carryover, and the dependence among repeated measurements. The official title describes a randomised, cross-over efficacy phase, and the arm description refers to an 8-spray sequence for participants titrated to 200 or 400 μg. However, the registry’s structured fields describe a single-group model and allocation as not applicable, and the record warns that this is not a randomized comparison. The registry does not provide enough detail to determine how the cross-over description was implemented or modeled.
In general, double-blinding means that treatment assignment is concealed from participants and relevant study personnel as specified by the protocol. The masking field is listed as double. The record does not identify exactly which roles were masked, how masking was maintained, or whether treatment guesses were assessed. Those details are not reported in the registry record.
What does the sample-size illustration mean?
In general, planning calculations can estimate how many participants per arm would be needed to detect an effect under specified assumptions. The registry’s planning description characterizes its calculations as illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation; it also distinguishes participant counts per arm from event totals for time-to-event outcomes. Such illustrations are not the trial’s observed power and do not establish that the trial was designed with those assumptions. The actual numerical planning outputs are not included in the record details summarized for this analysis, and the trial’s own sample-size justification is not reported in the registry record.
In general, observed power calculated after a study is completed is not a substitute for the estimate and confidence interval. Interpretation should focus on the effect estimate, precision, and analysis assumptions rather than treating a planning illustration as evidence that a finding is reliable or unreliable. The primary estimate and its interval are not reported in the registry record.
Why do missing details matter?
A complete statistical interpretation depends on knowing the model, the analysis population, the handling of repeated episode measurements, and the treatment of missing observations. The registry defines the Full Analysis Set, but it does not state the number included in that set, the number excluded, or the reasons for missing measurements. It does not report the detailed model specification, the approach to multiplicity, or any interim analyses. These omissions prevent assessment of whether the posted endpoint estimate, if available, would depend on modeling or missing-data assumptions.
More generally, over-dispersion occurs when observed variability is greater than a model assumes. If relevant, ignoring it can make standard errors too small and intervals too narrow. This is a general statistical consideration, not a reported feature of this trial: the registry does not identify over-dispersion or say whether it was assessed. In the absence of the full statistical plan and numerical primary result, the endpoint definition can be explained, but the analysis cannot be independently evaluated in detail.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and several secondary outcomes. The secondary outcomes include nasal mucosa sign or abnormality changes, pain intensity differences at additional time points, sums of pain intensity differences, episode response thresholds based on point or percentage reductions, general impression, and adverse events. Considering multiple outcomes, time points, thresholds, or analyses can increase the chance of a nominally unusual result arising by chance when many statistical tests are performed. In general, multiplicity procedures can control that risk, but the registry record does not report whether any adjustment was planned or used.
The record states that there was 1 analysis and 8 outcome measures. These counts do not identify the full set of hypotheses, whether analyses were prespecified, or how multiplicity was addressed. The statistical analysis plan and details of any interim analyses are not reported in the registry record. The record’s listed primary endpoint therefore cannot be assumed to be the only inferential test or to have been adjusted for the other outcomes.
The Full Analysis Set is defined as participants randomly assigned who entered the Efficacy Phase and received double-blind intranasal fentanyl for at least 1 breakthrough pain episode. The size of that set is not reported in the registry record. Nor does the record explain how participants with missing pain ratings, incomplete treatment sequences, or unavailable episode assessments were handled. In general, missing-data methods can affect estimates when the probability of missingness is related to measured or unmeasured outcomes. The registry does not provide enough information to evaluate that possibility or identify a missing-data assumption.
Enrollment of 46 participants is reported, but this is not necessarily the number contributing to the primary endpoint. The registry does not report participant flow or the number analyzed for each outcome. Consequently, the representativeness of the analysis population and the possible impact of missing observations cannot be assessed from the posted record.
11. 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 |
|---|---|---|---|
| Titration Phase | 2 | 45 | 4.4% |
| Efficacy Phase | 2 | 15 | 13.3% |
| Tolerability Phase | 8 | 31 | 25.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Titration Phase | 22 of 45 |
| Efficacy Phase | 5 of 15 |
| Tolerability Phase | 17 of 31 |
Most frequent serious adverse event terms
| Event term | Organ system | Titration Phase | Efficacy Phase | Tolerability Phase |
|---|---|---|---|---|
| Malignant neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 45 | 0 of 15 | 2 of 31 |
| Respiratory depression | Respiratory, thoracic and mediastinal disorders | 0 of 45 | 1 of 15 | 1 of 31 |
| Cardiovascular insufficiency | Cardiac disorders | 0 of 45 | 1 of 15 | 0 of 31 |
| Device occlusion | General disorders | 0 of 45 | 0 of 15 | 1 of 31 |
| Disease progression | General disorders | 0 of 45 | 0 of 15 | 1 of 31 |
| Jaundice | Hepatobiliary disorders | 1 of 45 | 0 of 15 | 0 of 31 |
| Femur fracture | Injury, poisoning and procedural complications | 0 of 45 | 0 of 15 | 1 of 31 |
| Metastases to lung | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 45 | 0 of 15 | 1 of 31 |
| Depression | Psychiatric disorders | 0 of 45 | 0 of 15 | 1 of 31 |
| Azotaemia | Renal and urinary disorders | 0 of 45 | 0 of 15 | 1 of 31 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Titration Phase | Efficacy Phase | Tolerability Phase |
|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 10 of 45 | 1 of 15 | 8 of 31 |
| Dizziness | Nervous system disorders | 8 of 45 | 2 of 15 | 4 of 31 |
| Vomiting | Gastrointestinal disorders | 3 of 45 | 1 of 15 | 4 of 31 |
| Fatigue | General disorders | 3 of 45 | 1 of 15 | 1 of 31 |
| Abdominal pain upper | Gastrointestinal disorders | 1 of 45 | 1 of 15 | 2 of 31 |
| Headache | Nervous system disorders | 1 of 45 | 0 of 15 | 3 of 31 |
| Nasal discomfort | Respiratory, thoracic and mediastinal disorders | 1 of 45 | 0 of 15 | 3 of 31 |
| Diarrhoea | Gastrointestinal disorders | 3 of 45 | 0 of 15 | 0 of 31 |
| General physical health deterioration | General disorders | 2 of 45 | 0 of 15 | 1 of 31 |
| Pyrexia | General disorders | 1 of 45 | 0 of 15 | 2 of 31 |
Serious events with the highest arm-level rate: cardiovascular insufficiency (6.7%), respiratory depression (6.7%), malignant neoplasm progression (6.5%), device occlusion (3.2%), disease progression (3.2%).
The registry presents serious and other adverse-event counts separately for the Titration, Efficacy and Tolerability Phases. The number at risk and the number affected are 45 and 2 for serious events, and 45 and 22 for other events, in the Titration Phase. In the Efficacy Phase the corresponding figures are 15 and 2, and 15 and 5. In the Tolerability Phase they are 31 and 8, and 31 and 17. These are phase-specific reported counts; they should not be added together or treated as a direct comparison between treatment groups.
The top serious-event terms listed are cardiovascular insufficiency and respiratory depression, each reported as 6.7%; malignant neoplasm progression, 6.5%; and device occlusion, disease progression and femur fracture, each 3.2%. The registry record does not identify the denominator for these term percentages in the posted information, so their rates cannot be reinterpreted as risk estimates for a clearly specified population.
Deaths are not reported in the registry record. The phase counts do not establish that a treatment caused an event, nor do they permit a controlled comparison of safety between intranasal fentanyl and placebo. The populations at risk differ by phase, and the design record cautions against treating arms as like-for-like controls.
12. What the Result Does, and Does Not, Mean
The registry record establishes what the trial intended to measure: change in pain intensity 10 minutes after the first dose during breakthrough pain episodes, using an 11-point rating scale. It defines a positive pain intensity difference as a reduction in pain and identifies a reduction of at least 2 points as clinically important. It also describes dose titration across 50, 100, 200 and 400 μg and includes objectives related to safety and nasal tolerability.
Those definitions do not tell the reader what occurred in the primary analysis. The numerical least-squares mean, 95% confidence interval, and primary-result p-value are not reported in the registry record. It is therefore not possible to state how much the pain rating changed, how uncertain that estimate was, or whether it met the stated clinical-importance threshold. The absence of the result in the registry record is not evidence of no effect; it is a limit on what can be concluded from the posted information.
The design details also constrain interpretation. The title describes a randomized, double-blind, placebo-controlled, cross-over phase, but the structured fields classify the study as single-group with allocation not applicable, and the registry cautions that the arms are not a like-for-like control comparison. The available description does not resolve this difference. A conventional treatment-versus-control effect should not be inferred from the record’s design labels alone.
The safety counts describe events across phases with differing numbers at risk. They provide a record of reported events, but do not by themselves identify comparative safety or causal relationships. The serious-event term percentages also lack a stated denominator in the posted information. In general, a trial’s findings apply most directly to its enrolled and analyzed population, but the number in the Full Analysis Set and participant flow are not reported.
The appropriate conclusion is limited: the record describes a Phase 3 study and its intended primary endpoint and safety aims, but does not report the primary numerical result needed to judge the observed pain outcome. It also omits details needed to resolve design and analysis questions. No treatment-effect conclusion should be drawn from the endpoint definition or adverse-event counts alone.
13. Why This Trial Matters Statistically
This trial illustrates why a clearly defined endpoint is not the same as a reported result. The registry describes a concrete measure: change in pain intensity from baseline to 10 minutes, on a defined rating scale, with a stated clinical-importance threshold. Such detail helps readers understand the intended estimand and the direction of improvement. But without the estimated change and its confidence interval, the observed effect and its precision remain unknown.
It also highlights the statistical importance of matching the analysis to the design. A cross-over description implies within-participant treatment sequences and repeated observations, while the structured record identifies a single-group model and warns against a like-for-like comparison of arms. Those distinctions matter because the choice of model, treatment of period and sequence effects, and handling of correlated episodes can affect the interpretation. The registry does not provide enough information to assess those choices.
The multiple outcomes, time points and response definitions listed in the record raise a further general issue: interpreting several tests requires attention to multiplicity and prespecification. The record does not report whether a multiplicity strategy was used. Likewise, a defined Full Analysis Set is helpful, but its size, participant flow and missing-data handling are not stated.
For clinical researchers and statisticians, this case shows that design labels, endpoint definitions, and safety counts each answer different questions. A phase-specific event count is not a comparative effect estimate, and a stated clinical threshold is not proof that the result crossed it. Statistical interpretation depends on the estimate, its uncertainty, the analysis population, and a sufficiently clear account of the design. The posted record supplies several of those definitions but not the primary numerical findings or key analysis details.
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 primary limitation is that the numerical result for the primary pain endpoint is not reported in the registry record. Without the least-squares mean and its 95% confidence interval, the magnitude and precision of the pain intensity difference cannot be evaluated. The record also does not report a primary-result p-value, so statistical significance cannot be assessed from the posted information.
The design descriptions are not fully aligned. The official title describes a placebo-controlled, double-blind, randomised, cross-over phase, and the arm description refers to randomization to an 8-spray sequence for some participants. The structured design fields instead list a single-group model and allocation as not applicable, with an explicit caution that this is not a randomized comparison and arms are not like-for-like controls. The available record does not reconcile these descriptions or provide the full treatment sequence.
The primary outcome title refers to the “Induction Phase,” while its timeframe and description refer to the Efficacy Phase. This difference in terminology is not explained. Further limitations include the absence of a reported sample-size justification, detailed statistical analysis plan, multiplicity approach, interim analysis information, analysis-set size, participant flow, and missing-data methods. The registry does not describe the model used to account for episode-level repeated measurements.
The safety data are presented by phase, with different numbers at risk, and the denominators for the listed serious-event percentages are not identified in the posted information. Deaths are not reported in the registry record. These features prevent direct between-phase or between-treatment risk comparisons. Taken together, the record permits a description of intended outcomes and reported phase-specific event counts, but not a complete efficacy or comparative safety assessment.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Clinical Trial With Intranasal Fentanyl in Cancer Patients With Breakthrough Pain — NCT01429051.
- Registry record last updated 2014-03-26; status last verified 2014-02.
- Results first posted 2014-03-26.
- 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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18. Record Summary
This completed Phase 3 trial enrolled 46 participants and studied dose-titrated intranasal fentanyl spray for breakthrough pain in cancer patients. The stated primary endpoint was pain intensity difference 10 minutes after the first dose, measured on an 11-point Numerical Rating Scale. The record defines a positive difference as reduced pain and identifies a reduction of at least 2 points as clinically important.
The official title describes a placebo-controlled, double-blind, randomised, cross-over efficacy phase and a 12-week safety and nasal tolerability evaluation. Structured design fields classify the study as single-group with allocation not applicable, and the record cautions that this is not a randomized comparison. The primary numerical estimate and its confidence interval are not reported in the registry record. Safety counts are listed separately for Titration, Efficacy and Tolerability phases, but do not support a direct controlled comparison. The record does not report key details including the sample-size justification, full statistical plan, analysis-set size, or missing-data handling.