An Efficacy and Safety Study to Compare Fentanyl Ionsys and Routine Care With Intravenous (IV) Morphine Patient-controlled Analgesia (PCA) in Participants Who Have Undergone Elective Major Abdominal or Orthopedic Surgery: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy and Safety Study to Compare Fentanyl Ionsys and Routine Care With Intravenous (IV) Morphine Patient-controlled Analgesia (PCA) in Participants Who Have Undergone Elective Major Abdominal or Orthopedic Surgery (NCT00766506), a randomized phase 4 study. The primary outcome is Participant's Evaluation of Mean Ability to Mobilize After Surgery.

2. Clinical Question

The clinical question is whether participants who have undergone elective major abdominal or orthopedic surgery report different ability to mobilize when receiving fentanyl IONSYS or routine care with morphine IV patient-controlled analgesia (PCA). The outcome focuses on interference attributed to the system or device: careful use of the hands, difficulty adjusting position in bed, and interference with getting out of bed and walking around.

The comparison concerns the experience of using the pain-control systems during early postoperative recovery, rather than pain intensity alone. The registry also lists safety, ease of care, pain ratings, rescue medication, and other recovery-related measures among the study’s interests. The primary mobility outcome was assessed at Hour 72 or at early study withdrawal.

The registry identifies the study as randomized, open-label, and parallel-group. Because masking was absent, participants and clinical staff knew which system was being used. That matters when interpreting a participant-reported outcome: the score records the participant’s assessment, and the record does not describe masking that might reduce awareness of treatment assignment.

3. Trial Design

The registry describes a phase 4, randomized, open-label, parallel-group study sponsored by Janssen-Cilag Ltd. It enrolled 108 participants and compared Fentanyl IONSYS with Morphine IV PCA after elective major abdominal or orthopedic surgery. The registry lists the study status as terminated. The reason for termination is not reported in the registry record.

Participants were assigned to one of the two study arms. The posted primary outcome data include 58 participants in the Fentanyl IONSYS arm and 50 in the Morphine IV PCA arm. The record’s definition of the primary analysis population requires random assignment, at least one use of study medication, and at least one efficacy measure after the system was applied or the device enabled. It therefore describes an analysis population with those conditions, rather than simply specifying that every randomized participant was included regardless of treatment use or outcome availability.

The registry describes the IONSYS arm as receiving fentanyl through an iontophoretic transdermal system. The Morphine IV PCA arm used intravenous morphine through a patient-controlled pump, with dosing set at the physician’s discretion within the stated maximum. The study was unmasked: the registry lists masking as none. The record does not describe a blinded assessment of the participant-reported primary outcome.

The primary outcome was a continuous score measuring perceived interference with mobilization, assessed at Hour 72 or early study withdrawal. Secondary measures listed in the registry include pain intensity, nurse ease of care, patient global assessment of pain control, time to fit for discharge, and medication use. The registry also records adverse-event information. The original sample-size justification, the reason for termination, and fuller details of the statistical analysis plan are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The intention-to-treat (ITT) population included all participants randomly assigned to study treatment and used the study medication at least once, and who had at least 1 efficacy measure after system application or device enablement (0 hours).

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 Participant's Evaluation of Mean Ability to Mobilize After Surgery, measured over Hour 72 or early study withdrawal.

The primary endpoint is the participant’s evaluation of mean ability to mobilize after surgery. It combines responses to three questions about whether the assigned system required care when using the hands, made it difficult to adjust position in bed, or interfered with getting out of bed and walking around. Each item uses a six-point Likert scale, with scores from 0, “not at all,” to 5, “a very great deal.” The endpoint is the average of the three item scores and ranges from 0, best mobility, to 5, worst mobility.

This measure is used to capture a practical aspect of early recovery: whether the pain-control device itself is perceived to hinder movement. That question is distinct from whether the participant has pain, how much pain is reported, or when the participant becomes fit for discharge. It complements those other outcomes by focusing on the interaction between the device and ordinary movement after surgery.

The assessment was scheduled for Hour 72 or early study withdrawal. The registry defines the primary analysis population as participants randomly assigned to treatment who used study medication at least once and had at least one efficacy measure after system application or device enablement. The endpoint is participant-reported, and the trial was unmasked. Its meaning is therefore a report of perceived device interference in this study population, not an objective measure of walking ability or a general measure of postoperative recovery.

7. Results Posted in the Registry

• Morphine IV PCA: mean 2.26 versus 0.02 on control; difference 2.24 (95% CI 1.92 to 2.56), standardized effect d = 2.86; z-test p = <0.001.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Nurse Ease of Care (EOC) Questionnaire Score

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Morphine IV PCA: mean 0.80 versus 0.28 on control; difference 0.52 (95% CI 0.19 to 0.85), standardized effect d = 0.61; z-test p = 0.002.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for Morphine IV PCA than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Number of Participants Who Require Rescue Medication

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Morphine IV PCA: 4.0% (2/50) versus 17.2% (10/58) on control; risk difference -13.2 percentage points (95% CI -24.4 to -2.1), risk ratio 0.23 (0.05–1.01); unadjusted two-proportion z-test p = 0.029.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically lower for Morphine IV PCA than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes provide a mixed but limited picture of recovery and treatment use. The posted nurse ease-of-care result points in the same broad direction as the primary device-interference score: its average is lower in the Fentanyl IONSYS group than in the Morphine IV PCA group. The rescue-medication result differs in direction, with more participants recorded as requiring rescue medication in the Fentanyl IONSYS arm during the stated early assessment period. These outcomes measure different aspects of care and should not be collapsed into a single judgment about treatment performance.

The registry also lists pain intensity, patient global assessment of pain control, time to fit for discharge, use of concomitant antiemetic medication, and use of concomitant non-opioid analgesics. Their results are not reported in the registry record. Consequently, the posted secondary data do not establish a consistent pattern across every listed aspect of pain, care, and recovery. In particular, the reported mobility finding cannot substitute for unreported results on pain intensity or readiness for discharge.

Secondary outcomes are generally interpreted with less weight when many outcomes are examined and no multiplicity procedure is reported. Testing multiple outcomes increases the opportunity for a result to appear statistically notable by chance. The registry record does not report an adjustment for multiple comparisons or identify a hierarchy that would establish which secondary measures were confirmatory. The secondary findings can add context and generate questions, but they should not be treated as independent confirmation of the primary endpoint or as a complete account of recovery.

The number of listed outcome measures and analyses is not itself evidence that every result is available or that every comparison was planned as a formal hypothesis test. The registry reports selected analyses, while results for several listed secondary endpoints are not reported. Interpretation should therefore remain attached to the particular outcome, assessment period, and analysis that are actually posted.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Pain Intensity Numerical Rating Scale (NRS)
• Nurse Ease of Care (EOC) Questionnaire Score
• Number of Participants With Patient Global Assessment (PGA) of Method of Pain Control
• Time to Fit For Discharge (FFD)
• Number of Participants Who Require Rescue Medication
• Number of Participants Who Require Concomitant Antiemetic Medication
• Number of Participants Who Require Concomitant Non-opioid Analgesics

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is a continuous measure: it is an average score on a bounded scale, not a count of participants or an event rate. The registry reports a mean and standard deviation for each treatment group. A mean describes the group’s average score, while the standard deviation describes how dispersed individual scores are around that average. Lower scores on this particular scale indicate less perceived device interference and better mobility.

What does the mean difference describe?

The unadjusted recalculation compares the group means by subtracting the Fentanyl IONSYS mean from the Morphine IV PCA mean. This gives a mean difference of 2.24. Because the scale is oriented so that higher scores indicate worse mobility, a positive difference in that order means the Morphine IV PCA group had a higher average interference score. The estimate is an unadjusted comparison of the posted group summaries; it does not account for covariates.

The registry also reports an ANCOVA result as a least squares mean difference of -2.23. ANCOVA is a model-based method for comparing group means while accounting for covariates included in the model. The registry record does not report the covariates or further model specifications, so the adjustment cannot be independently described in detail. The negative sign reflects the reported group ordering, which is opposite to the ordering used for the unadjusted recalculation. Reversing the order changes the sign, not the underlying direction of the comparison.

How should the p-values be read?

A p-value measures how compatible the observed result is with a model in which there is no group difference, under the assumptions used for that test. It is not the probability that a treatment works, nor does it measure the size or practical importance of a difference. For the primary outcome, both the reported ANCOVA analysis and the unadjusted recalculation have p-values below 0.001. The registry reports the ANCOVA as its analysis; the recalculated p-value is an unadjusted check based on the posted summary statistics.

The nurse ease-of-care result is also continuous. The unadjusted recalculation compares the posted least squares means and yields a mean difference of 0.52 in the Morphine IV PCA minus Fentanyl IONSYS ordering. The sponsor-reported ANCOVA result is -0.52 in the opposite group order, with p <0.001. The record indicates that the posted group summaries for this endpoint use least squares means and 95% confidence intervals; the recalculated comparison is marked as using an approximate pooled standard deviation. These summaries should not be confused with the primary endpoint analysis.

What is different about the rescue-medication comparison?

Rescue medication is recorded as a binary outcome: each participant either required rescue medication in the stated period or did not. The registry posts 10 participants in the Fentanyl IONSYS group and 2 in the Morphine IV PCA group who required rescue medication from baseline up to Hour 3. It reports an odds ratio of 5.00, with a 95% confidence interval from 1.04 to 24.03, and a chi-squared p-value of 0.029. An odds ratio compares the odds of the event between groups; its direction depends on which group is placed first. The record does not state that this endpoint was adjusted for covariates.

The unadjusted recalculation for the binary outcome also reports a risk difference of -0.132, with a confidence interval from -0.244 to -0.021, using its stated group ordering. A risk difference describes the difference between event proportions, whereas an odds ratio compares odds. They are different measures, so their numerical values should not be treated as interchangeable. No new percentage or event count should be inferred from one measure when the registry has already stated the relevant comparison.

What does the registry analysis represent?

The posted primary analysis uses an intention-to-treat label, but its stated population definition includes participants who used study medication at least once and had at least one efficacy measure after system application or device enablement. This definition should be read as written. It does not establish how participants without a post-application measure were handled, or whether any other analysis population was used. Those details are not reported in the registry record.

The registry lists ANCOVA for the primary result and for nurse ease of care, and a chi-squared analysis for the rescue-medication result. It does not report the full statistical analysis plan, the covariates in the ANCOVA, the missing-data method, or any adjustment for multiple comparisons. Statistical interpretation should therefore distinguish the stated model-based results from the simple unadjusted recalculations and avoid assuming unreported analysis details.

11. Confidence Intervals and Precision

A confidence interval describes a range of values compatible with the observed data under the statistical method used. It conveys uncertainty about the estimated group difference; it is not a guarantee that the true difference lies within the interval, and it does not describe the range of individual participants’ scores. The confidence intervals attached to the primary and secondary analyses quantify uncertainty in the estimated comparisons.

For the primary endpoint, the unadjusted recalculated mean difference is 2.24, with a confidence interval from 1.921 to 2.559. The registry’s ANCOVA estimate is -2.23, with a 95% confidence interval from -2.55 to -1.91. The signs differ because the group ordering differs. Both intervals exclude zero, consistent with the reported p-values below 0.001. The interval widths indicate that the estimate is not a single exact value, even though the posted analyses point in the same direction.

For nurse ease of care, the reported ANCOVA difference is -0.52, with a 95% confidence interval from -0.74 to -0.30. The unadjusted recalculated estimate is 0.52 in the reverse group order, with a confidence interval from 0.194 to 0.847. The two analyses should be kept distinct because the sponsor’s result is model-based and the recalculation uses posted summaries.

The rescue-medication odds ratio has a 95% confidence interval from 1.04 to 24.03. This interval spans a broad range of effect sizes, so the point estimate alone would give an incomplete impression of precision. The confidence interval for the risk difference likewise runs from -0.244 to -0.021 in the recalculation’s group order. The record does not report confidence intervals for the unreported secondary outcomes.

Confidence intervals address sampling uncertainty under a specified analysis; they do not address all possible sources of uncertainty. In this trial, interpretation is also limited by the open-label design, participant-reported primary outcome, unreported covariate details, and the absence of reported missing-data and multiplicity procedures.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations based on the observed effects, not the trial’s original design assumptions. For these continuous and binary outcomes, the figures are participants per arm. A time-to-event planning table, if one were used, would instead report total events, but the posted planning figures described for these outcomes are per arm.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as a stated fraction of the observed effect. The table gives separate targets for planning for 80% power and 90% power. In plain terms, power is the chance that a study would detect an effect of the specified size under the planning assumptions if that effect were present. The 90% target is designed for a higher chance of detection than the 80% target, and therefore generally calls for more participants per arm.

The rows that use 100%, 75%, and 50% of the observed effect illustrate how the planned effect size changes the required sample. A smaller effect is harder to distinguish from random variation, so detecting it requires more participants per arm under the same assumptions. The figures are not a reconstruction of the enrollment target or evidence that the completed trial was adequately powered.

These calculations are not observed power. They are forward-looking planning illustrations that use the observed effect as an input; they do not measure the probability that the completed trial’s result is true. The original sample-size justification and planning assumptions are not reported in the registry record.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = 2.240; pooled standard deviation σ = 0.783.
2. n = 2 × (1.96 + 0.842)² × 0.783² / 2.240² = 1.9, rounded up to 2 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- 2.24                      # observed difference in means
sigma <- 0.78267767890531                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(766506)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2 (80% power), 3 (90% power)
 75% of observed effect: n per arm = 4 (80% power), 5 (90% power)
 50% of observed effect: n per arm = 8 (80% power), 11 (90% power)
power.t.test: 3.2 
Simulated power at n = 2 per arm: 0.365 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry’s sponsor-reported primary analysis is ANCOVA, expressed as a least squares mean difference of -2.23, with a 95% confidence interval from -2.55 to -1.91 and p <0.001. The unadjusted recalculation from the posted group means expresses the difference in the reverse order and gives 2.24, with a confidence interval from 1.921 to 2.559 and an unadjusted p-value below 0.001. The opposing signs reflect reversed group ordering, not opposing conclusions about the direction of the score comparison.

The two estimates are close in magnitude, but they are not the same analysis. The recalculation is a simple comparison of posted summaries and does not incorporate model adjustment. The ANCOVA is the analysis reported by the registry as the sponsor’s result. The record does not identify the ANCOVA covariates or provide enough detail to reproduce that model, so the recalculation should be read as a descriptive cross-check rather than a replacement for the reported analysis.

The same distinction applies to nurse ease of care: the reported ANCOVA difference is -0.52, while the unadjusted recalculation is 0.52 in the reverse group order. For rescue medication, the registry reports a chi-squared analysis and odds ratio, while the recalculation presents unadjusted binary comparisons. No discrepancy between the recalculated and reported results is flagged in the registry record.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study examines several outcomes or makes several statistical comparisons. Even when each test uses a conventional significance threshold, conducting many tests increases the chance that at least one result will appear statistically notable by chance. A multiplicity procedure can control that risk, for example by adjusting inference or by defining a prespecified hierarchy of outcomes. Such a procedure is not reported in the registry record.

The registry lists 10 outcome measures and 11 analyses. It identifies the participant-reported mobilization score as the primary outcome and names several secondary measures, including pain intensity, nurse ease of care, patient global assessment of pain control, time to fit for discharge, rescue medication, antiemetic medication, and non-opioid analgesics. Results are posted for some secondary comparisons, but results for several listed measures are not reported in the registry record. The record does not state whether a formal outcome hierarchy or multiplicity adjustment was used.

Missing-data handling is also not reported. The primary outcome is assessed at Hour 72 or early study withdrawal, and the stated intention-to-treat population requires at least one efficacy measure after system application or device enablement. This definition gives information about who qualifies for that analysis population, but it does not explain what happened to participants without a post-application measure, how incomplete item responses were handled, or whether any imputation was used.

The registry’s use of the intention-to-treat label should therefore be considered alongside its operational population definition. The record does not describe an analysis of all randomized participants regardless of medication use and outcome availability. Nor does it report sensitivity analyses that would show how conclusions might change under alternative assumptions about missing outcomes.

The primary endpoint is participant-reported and the study was unmasked, which may matter to interpretation, but the registry does not describe procedures intended to address that concern. It also does not report the full statistical analysis plan, the ANCOVA covariates, interim analyses, or the original sample-size justification. These omissions do not negate the posted estimates; they limit how fully the analysis choices and robustness can be evaluated.

16. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: wound infection (2.0%), femur fracture (2.0%), pulmonary embolism (2.0%), haematoma (1.7%).

The registry reports serious adverse events affecting 1 participant in the Fentanyl IONSYS group and 2 participants in the Morphine IV PCA group. The corresponding groups at risk were 58 and 50. These are counts of participants affected, not a complete description of the nature, timing, or causal relationship of every event. The registry also reports other adverse events affecting 40 participants in the Fentanyl IONSYS group and 38 in the Morphine IV PCA group.

The record lists wound infection, femur fracture, pulmonary embolism, and haematoma among the top serious-event terms, with percentages of 2.0%, 2.0%, 2.0%, and 1.7%, respectively. It does not specify in this listing which treatment group each term belongs to. Death figures are not reported in the registry record.

These figures describe events recorded during the study; they do not by themselves establish that a treatment caused an event or provide a complete comparative safety assessment. The record does not provide enough detail to assess event timing, exposure-adjusted rates, severity beyond the serious-event classification, or the criteria used for attribution. The study’s status is terminated, and the reason for termination is not reported in the registry record.

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

The posted primary result means that participants in the Fentanyl IONSYS group had a lower average score on the device-interference mobility scale than participants in the Morphine IV PCA group. The scale runs from 0, best mobility, to 5, worst mobility. The reported ANCOVA estimate and the unadjusted recalculation point in the same direction after accounting for their reversed group ordering. The reported confidence interval is separated from zero, and the reported p-value is below 0.001.

This finding is about participants’ assessments of how the pain-control system affected movement. It does not directly establish differences in pain relief, surgical recovery overall, ability to walk as objectively measured, or time to discharge. The registry lists those and other outcomes, but results for several are not reported. A lower interference score should not be used as a substitute for evidence on outcomes that were not posted.

The result also does not establish that either approach is universally preferable or that the observed comparison applies to settings beyond participants undergoing elective major abdominal or orthopedic surgery in this trial. The study was open-label, and the primary endpoint was participant-reported, so awareness of the assigned device is relevant context. The registry does not report the covariates in the ANCOVA or the handling of missing outcome data, which limits independent evaluation of those analysis details.

The rescue-medication result is a separate finding: the posted count was higher in the Fentanyl IONSYS group during the stated period, and the reported odds-ratio confidence interval is broad. It should not be combined with the mobility score as if the outcomes measured the same thing. Nurse ease of care is another distinct measure, while unreported secondary results cannot be inferred from the primary result.

Overall, the record supports a narrow statistical interpretation of the reported primary score and selected secondary analyses. It does not support a general claim about all dimensions of pain management, safety, or postoperative recovery, nor does statistical evidence alone determine clinical importance.

18. Why This Trial Matters Statistically

This trial illustrates why an endpoint’s scale and direction must be understood before interpreting a group difference. The primary score is not a pain-intensity score: it measures perceived interference with mobilization, and lower values represent better mobility. The group ordering also matters. The unadjusted recalculation expresses the difference as Morphine IV PCA minus Fentanyl IONSYS, while the reported ANCOVA uses the opposite direction. The signs therefore differ even though the analyses point to the same direction of group contrast.

It also shows the value of separating a sponsor-reported model from an unadjusted recalculation. ANCOVA can account for specified covariates, but the registry does not identify them. A recalculation from group summaries can check the broad numerical consistency of a result, but it cannot reproduce an analysis whose model details are absent. Neither estimate should be described without clarifying what was compared and how.

The participant-reported endpoint and open-label design make measurement context important. The score captures perceived interference by a known device, not an assessor-blinded or objective mobility test. That does not make the measure irrelevant; it defines what the result means and what it cannot answer.

Finally, the record highlights the difference between a statistically notable result and a complete clinical account. Several secondary outcomes are listed, but their results are not reported, and multiplicity handling is not described. Confidence intervals show uncertainty around reported estimates, while unreported outcomes, missing-data procedures, and analysis-plan details remain additional limits. These distinctions help keep conclusions proportionate to the evidence in the registry record.

19. 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 study was open-label, and the primary endpoint relied on participants’ reports about whether their assigned device interfered with movement. Awareness of treatment assignment could influence such assessments. The registry does not describe masking of outcome assessment or other procedures to reduce that possibility.

The registry defines the primary analysis population using treatment use and availability of at least one post-application efficacy measure. It does not report how missing primary scores were handled, whether incomplete questionnaire items were included, or what sensitivity analyses were performed. The reason for study termination is not reported in the registry record.

The sponsor-reported primary result uses ANCOVA, but the covariates and detailed model specification are not reported. The original sample-size justification and statistical analysis plan are also not reported. Although planning illustrations based on observed effects are available, they do not establish the assumptions used to design this trial.

The results posted for secondary outcomes are incomplete relative to the outcomes listed. In particular, the registry does not report results for several recovery and medication-use measures. It also does not report a multiplicity adjustment, making isolated secondary p-values harder to interpret as confirmatory evidence.

The safety summary gives affected-participant counts and selected serious-event terms, but does not provide a complete account of timing, attribution, or exposure-adjusted comparisons. Death figures are not reported in the registry record. The study population and surgical settings described in the record also limit the scope of interpretation; results should not be assumed to apply to populations or procedures not described.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: An Efficacy and Safety Study to Compare Fentanyl Ionsys and Routine Care With Intravenous (IV) Morphine Patient-controlled Analgesia (PCA) in Participants Who Have Undergone Elective Major Abdominal or Orthopedic Surgery — NCT00766506.
• Registry record last updated 2013-04-25; status last verified 2013-03.
• Results first posted 2013-04-25.
• 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.

23. Record Summary

NCT00766506 is a randomized, open-label, phase 4, parallel-group study comparing Fentanyl IONSYS with Morphine IV PCA after elective major abdominal or orthopedic surgery. The registry lists enrollment of 108 and study status as terminated; the reason for termination is not reported in the registry record.

The primary outcome is a participant-reported average score for device interference with mobilization, assessed at Hour 72 or early study withdrawal. The posted group means are 0.02 for Fentanyl IONSYS and 2.26 for Morphine IV PCA. The reported ANCOVA difference is -2.23, with a 95% confidence interval from -2.55 to -1.91 and p <0.001; the unadjusted recalculation uses the reverse group ordering and points in the same direction.

Some secondary results and adverse-event counts are posted, while results for several listed secondary measures and details of missing-data, multiplicity, and model procedures are not reported in the registry record.