An Interventional Study to Compare the Efficacy and Tolerability With Targin® in Non-malignant Chronic Pain (GLORY): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Interventional Study to Compare the Efficacy and Tolerability With Targin® in Non-malignant Chronic Pain (GLORY) (NCT01811186), a randomized phase 4 study. The primary outcome is Drop-out Rate Caused by Adverse Event After 6 Weeks Treatment.

2. Clinical Question

GLORY is a randomized, parallel-group phase 4 study with no masking. Its registered objective of main interest was adverse-event-related drop-out after 6 weeks. The comparison is therefore about tolerability as represented by this particular outcome, not a comprehensive measure of every possible benefit or harm. Pain intensity, quality of life and satisfaction were also listed as further objectives.

The registry record describes the study as completed. It lists enrollment of 261 and an intent-to-treat primary analysis set of 258 patients using Last Observation Carried Forward. The outcome summaries report 132 participants in the 10/5mg starting group and 126 in the 5/2.5mg starting group. These are the denominators shown for the primary outcome, and the registry’s stated analysis population is the relevant context for interpreting its result.

3. Trial Design

GLORY (NCT01811186) is registered as an interventional, randomized, parallel-group phase 4 study of oxycodone/naloxone in non-malignant chronic pain. The registry records no masking. Thus, the comparison is described as randomized but open-label: participants and study personnel were not masked to the assigned schedule according to the registry entry. The sponsor is Mundipharma Korea Ltd.

The two groups used different starting doses and escalation sequences. Group A began at 10/5mg twice daily and was scheduled to titrate through 20/10mg, 30/15mg and 40/20mg twice daily. Group B began at 5/2.5mg twice daily and was scheduled to titrate through 10/5mg, 20/10mg, 30/15mg and 40/20mg twice daily. Both are described as oxycodone/naloxone regimens. The record gives these schedules but does not report whether individual participants reached each step or how closely treatment followed the intended sequence.

The registered study start is 2012-12, primary completion is 2014-01, and status is completed. Enrollment is 261. The primary outcome analysis is described as an intent-to-treat analysis set of 258 patients, with Last Observation Carried Forward. Outcome-specific denominators differ across the reported measures, so each result should be read with its own stated denominator rather than assuming the same number of observations contributed to every outcome.

The primary objective was to assess drop-out caused by an adverse event after 6 weeks. Further objectives included drop-out due to an adverse event after 1 week, pain reduction, EQ-5D quality of life, investigator and subject satisfaction, and safety. The registry record does not report the trial’s original sample-size justification or its full statistical analysis plan. It also does not report details about adherence to the dose-escalation schedules or the masking of any outcome assessment.

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: Intent to treat analysis set: 258 patients (Last Observation Carried Forward)

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: Safety set: 261 ITT set: 258(3 patients were deviated inclusion/exclusion criteria among 261)

6. Primary Endpoint

The registry lists the primary outcome as Drop-out Rate Caused by Adverse Event After 6 Weeks Treatment, measured over 6 weeks.

The primary endpoint is the drop-out rate caused by an adverse event after 6 weeks of treatment. It is expressed as a percentage of participants. In this setting, the measure captures the proportion who discontinued treatment for the specified reason during the stated period. It is a focused tolerability outcome: it does not count every adverse event as a drop-out, and it does not by itself describe the severity or duration of symptoms among those who continued.

The registry describes the primary analysis population as an intent-to-treat set of 258 patients, using Last Observation Carried Forward. The group summaries report 40.91% for the 10/5mg starting schedule and 30.16% for the 5/2.5mg starting schedule. The accompanying event counts are 54 of 132 and 38 of 126, respectively. Those counts and denominators provide the basis for the unadjusted comparison reported with the outcome.

Drop-out due to an adverse event is used because discontinuation can signal that treatment was not tolerable enough for a participant to continue under the study conditions. However, interpretation depends on how drop-outs and adverse-event attribution were defined and assessed. Those operational details are not reported in the registry record. Nor does this endpoint alone establish the overall balance of tolerability, safety and symptom outcomes. It answers the narrower registered question about adverse-event-related discontinuation by 6 weeks.

7. Results Posted in the Registry

• Start Oxycodone/Naloxone 5/2.5mg b.i.d.: 30.2% (38/126) versus 40.9% (54/132) on control; risk difference -10.8 percentage points (95% CI -22.4 to 0.8), risk ratio 0.74 (0.53–1.03); unadjusted two-proportion z-test p = 0.072.

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.

The Change of Pain Intensity Scores(NRS) From Baseline After 6 Weeks Treatment With the Study.

• 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:
  • Start Oxycodone/Naloxone 5/2.5mg b.i.d.: mean -1.48 versus -1.62 on control; difference 0.14 (95% CI -0.31 to 0.59), standardized effect d = 0.08; z-test p = 0.546.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Start Oxycodone/Naloxone 5/2.5mg b.i.d. and the control. The interval gives the range of effects that remain compatible with the data.

Change of Quality of Life (EQ-5D) Score After 6 Weeks Treatment With the Study Drug

• 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:
  • Start Oxycodone/Naloxone 5/2.5mg b.i.d.: mean 0.07 versus 0.14 on control; difference -0.07 (95% CI -0.15 to 0.01), standardized effect d = -0.29; z-test p = 0.105.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Start Oxycodone/Naloxone 5/2.5mg b.i.d. and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes broaden the clinical questions beyond adverse-event-related discontinuation. They include change in pain intensity, change in EQ-5D quality-of-life score, investigator satisfaction, subject satisfaction and drop-out due to an adverse event after 1 week. The registry also identifies safety as a further objective. Numerical summaries are reported for pain intensity and EQ-5D; the registry record does not report numerical results for the other listed secondary outcomes in the information available for these comparisons.

Across the reported continuous outcomes, the mean changes are in the direction of improvement from baseline in both groups for pain intensity and EQ-5D. The group contrasts are modest relative to their uncertainty, and the confidence intervals for the mean differences include zero. These secondary findings do not provide a clear, precise contrast that resolves the primary drop-out comparison. They should be considered alongside, rather than substituted for, the primary tolerability outcome.

Secondary outcomes are useful for describing broader patterns and potential trade-offs, but they usually carry less weight when many outcomes are assessed without a clearly reported multiplicity plan. Testing multiple outcomes can increase the chance that at least one result appears noteworthy by chance. The registry record does not report whether a hierarchy, adjustment for multiple comparisons or prespecified emphasis among secondary outcomes was used. The reported secondary p-values are unadjusted, so they should be treated as exploratory rather than as stand-alone confirmatory evidence.

There are also differences in the number of observations contributing to outcomes. EQ-5D denominators are smaller than those reported for the primary analysis, while pain summaries use the primary outcome group denominators. Reasons for these differences and the handling of missing secondary measurements are not reported in the registry record. This makes it important to interpret each outcome using its own denominator and to avoid assuming that every result represents the same analysis population.

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

• The Drop-out Rate Due to an Adverse Event After 1 Week Treatment With the Study Drug.
• The Change of Pain Intensity Scores(NRS) From Baseline After 6 Weeks Treatment With the Study.
• Change of Quality of Life (EQ-5D) Score After 6 Weeks Treatment With the Study Drug
• Assessment of Investigator's Overall Satisfaction After 6 Weeks Treatment With the Study Drug
• Assessment of Subject's Overall Satisfaction After 6 Weeks Treatment With the Study Drug

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is binary at the participant level: a participant either contributes an adverse-event-related drop-out event or does not, according to the trial’s outcome definition. The registry presents the result as a percentage of participants, alongside the group denominators and event counts. A percentage is useful because it expresses the event frequency relative to the number assessed in each group. The registry record does not report the detailed operational definition of an adverse-event-related drop-out, including how attribution was determined.

What does randomization contribute?

In general, random allocation is intended to make comparison groups similar, on average, with respect to both measured and unmeasured characteristics before treatment begins. This can reduce confounding in a treatment comparison. Randomization does not guarantee that groups will be identical, particularly in a study of finite size, and it does not remove uncertainty in the estimated result. The record identifies allocation as randomized but does not describe the randomization sequence, concealment procedures or stratification factors.

The study is described as parallel and unmasked. In a parallel design, participants are assigned to one of the schedules and followed in that group; the record does not describe a crossover. In general, lack of masking can affect participant reports, treatment decisions or outcome assessment, depending on the outcome and study procedures. The registry does not describe whether outcome assessors were separately masked, nor does it report procedures intended to mitigate possible effects of open-label conduct.

How should the primary comparison be read?

The risk difference is the event proportion in one group minus the event proportion in the comparison group. Here the reported comparison is 5/2.5mg starting schedule minus 10/5mg starting schedule, with a recalculated estimate of -0.107. This signed quantity preserves direction: a negative estimate means the observed proportion was lower in the first-named group. It is an unadjusted comparison calculated from the posted group summary counts rather than a reported covariate-adjusted model.

The risk ratio compares the proportions by division, while the odds ratio compares the odds of the event. These measures express the same binary comparison on different scales. Their interpretation depends on which group is placed in the numerator, so the stated comparison direction matters. They do not constitute independent replications of the primary finding; they are alternative summaries of the same group data.

What do the confidence interval and p-value add?

In general, a confidence interval gives a range of effect estimates reasonably compatible with the observed data under the method used. Its width conveys precision: a wider interval means less precision. A confidence interval that includes the null value for the measure does not establish that the true effect is exactly null; it indicates that the data do not exclude that value at the interval’s stated confidence level. For a risk difference, the null value is zero. For a ratio measure, it is one.

A p-value describes how unusual data at least as inconsistent with the null hypothesis would be if the null hypothesis and the model assumptions held. It is not the probability that the null hypothesis is true, nor a measure of clinical importance. The unadjusted p-value for the primary comparison is 0.072, and the confidence interval crosses zero. Those results are consistent with uncertainty about the direction and size of the difference. The registry record does not report a sponsor model or adjusted inferential analysis for this comparison; the posted comparison is a simple unadjusted recalculation.

How do the continuous secondary outcomes differ?

Pain intensity and EQ-5D are reported as mean changes from baseline, with standard deviations. A mean summarizes the average change, while a standard deviation describes variation among participant values around that average. A mean difference compares the group averages. In general, a mean can conceal variation in individual responses, and its precision depends on both variability and the number of observations contributing to that outcome.

The pain comparison uses the reported group means and standard deviations. EQ-5D has its own outcome-specific denominators, which are smaller than the primary outcome denominators. The registry does not explain why fewer observations contribute to the EQ-5D summaries or how missing measurements were handled for those summaries. No reported inferential analyses are listed for the secondary measures; the displayed comparisons are recalculated, unadjusted comparisons based on the available summary statistics.

What is the role of the analysis population?

The primary outcome description identifies an intent-to-treat analysis set and specifies Last Observation Carried Forward. In general, intent-to-treat analysis aims to retain participants in their randomized groups, regardless of treatment changes or discontinuation, subject to the outcome and data available. Last Observation Carried Forward replaces a missing later measurement with the participant’s last recorded value. It is a simple imputation approach, but it can misrepresent uncertainty and may be biased if the carried-forward value is not a reasonable substitute for the missing outcome. The registry record does not report the missing-data reasons, the amount of missingness by group, sensitivity analyses, or whether this method was used for outcomes other than the primary analysis.

These methods explanations are general statistical context. The registry record does not report enough detail to reconstruct the full trial analysis, including model specifications, covariate adjustments, handling of protocol deviations or the original rationale for the sample size. The interpretation should therefore remain close to the reported summaries and their unadjusted uncertainty.

11. Confidence Intervals and Precision

The primary risk-difference estimate is -0.107, with a 95% confidence interval from -0.224 to 0.009. The point estimate favors a lower observed drop-out proportion in the 5/2.5mg starting group, but the interval includes zero. Thus, the posted data do not rule out no difference, and they also remain compatible with a range of differences in either direction. The interval’s span signals that the estimate is not highly precise.

The corresponding risk-ratio interval runs from 0.527 to 1.031, and the odds-ratio interval runs from 0.373 to 1.044. Each includes its no-difference value. These intervals express uncertainty on different scales; they should be interpreted with attention to their scale and the specified group order. They are based on the same outcome counts, not separate evidence.

For pain change, the mean difference is 0.14, with a 95% confidence interval from -0.314 to 0.594. For EQ-5D change, the mean difference is -0.07, with a 95% confidence interval from -0.155 to 0.015. Both intervals include zero. The EQ-5D summaries use 61 participants in the 10/5mg starting group and 64 in the 5/2.5mg starting group, compared with the larger denominators reported for the primary outcome. The registry record does not explain the smaller EQ-5D analysis denominators.

In general, a confidence interval is not a guarantee that the true effect lies within its endpoints. It describes uncertainty under the calculation’s assumptions. These intervals are recalculated from posted summary statistics, rather than presented as sponsor-reported model estimates. The registry record does not report a full statistical analysis plan that would clarify whether other analyses, adjustment methods or sensitivity checks were prespecified.

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 calculations. For these outcomes, the figures mean participants per arm, not total events. 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 the stated fraction of the observed effect. The original sample-size assumptions and justification are not reported in the registry record.

The 80% power column gives the number of participants per arm estimated to be needed for an 80% chance of detecting the specified effect under those planning assumptions, if that effect is real and the assumptions hold. The 90% power column gives the corresponding estimate for a 90% chance. Higher target power generally requires more participants. These are planning quantities, not observed power.

For the primary outcome, planning for 100% of the observed effect gives 310 participants per arm for 80% power and 415 for 90% power. Planning for 75% of the observed effect gives 561 participants per arm for 80% power and 751 for 90% power. Planning for 50% of the observed effect gives 1,282 participants per arm for 80% power and 1,716 for 90% power. The same pattern applies to the continuous outcomes: the smaller the effect targeted, the more participants the illustration requires. An effect smaller than the observed estimate is harder to distinguish from random variation, all else held constant.

These figures depend on the observed effect, which is uncertain, and they are not a reconstruction of the study’s planned enrollment. The registry record does not report the assumptions used when the trial was designed, so the illustrations should not be used to infer the study’s original power or intent.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.409; treatment proportion p₁ = 0.302; average p̄ = 0.355.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6769 = 1.3266.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6726 = 0.5661.
4. n = (1.3266 + 0.5661)² / (-0.1075)² = 310.0, rounded up to 310 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
p0 <- 0.409090909090909                          # control proportion
p1 <- 0.301587301587302                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(1811186)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 310 (80% power), 415 (90% power)
 75% of observed effect: n per arm = 561 (80% power), 751 (90% power)
 50% of observed effect: n per arm = 1,282 (80% power), 1,716 (90% power)
power.prop.test: 310 
Simulated power at n = 310 per arm: 0.799 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary objective of assessing adverse-event-related drop-out after 6 weeks and several further objectives, including a 1-week drop-out outcome, pain change, EQ-5D quality of life, satisfaction and safety. When a study evaluates multiple outcomes, the chance of at least one apparently unusual result can rise if each is tested separately without adjustment. Statistical approaches can address this concern by prespecifying an outcome hierarchy or adjusting inference across a family of comparisons. The registry record does not report a multiplicity procedure or explain which secondary comparisons, if any, were intended as confirmatory.

The primary comparison has an unadjusted p-value of 0.072. The secondary p-values for the reported pain and EQ-5D comparisons are also unadjusted. No reported analyses are listed for those secondary outcomes. Without a documented plan for handling multiple outcomes, these p-values should not be interpreted as if they were adjusted confirmatory tests. The direction and size of estimates, their confidence intervals and the scope of outcomes reported are more informative than treating a threshold crossing in isolation.

For the primary result, the registry states that the analysis population was an intent-to-treat set of 258 patients and that Last Observation Carried Forward was used. In general, this method fills a missing later observation with the last recorded value. It can be straightforward to implement, but it treats the carried-forward value as if it were an adequate representation of the missing result and does not itself account for uncertainty about what would have been observed. Its suitability depends on the outcome and reasons data are missing. The registry record does not report the amount or reasons for missing primary outcomes, whether missingness differed between groups, or sensitivity analyses using alternative assumptions.

The registry record also does not explain the smaller denominators for EQ-5D, or state the missing-data method for the secondary outcomes. It does not report the full statistical analysis plan, protocol deviations, analysis-set rules beyond the primary description, or any adjustments for baseline characteristics. These omissions limit assessment of whether the reported summaries reflect prespecified methods and how robust they are to missing data or alternative analytic choices. They do not demonstrate that any particular bias occurred; they mark information that is not reported in the registry record.

15. 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 1% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: duodenal stenosis (0.8%), inflammation (0.8%), femoral neck fracture (0.8%).

The serious adverse event figures are counts of affected participants over the stated at-risk denominators. In the 10/5mg starting group, the registry reports 0 serious adverse events among 133 at risk. In the 5/2.5mg starting group, it reports 2 among 128 at risk. These safety denominators differ from the primary outcome denominators, so the serious-event figures should not be substituted for or combined with the drop-out analysis.

The registry lists duodenal stenosis, inflammation and femoral neck fracture among the top serious event terms, each with a reported frequency of 0.8%. The record does not give enough detail to assign those terms to a particular group or to infer whether they were considered treatment-related. The death counts are not reported in the registry record.

These counts describe serious adverse events recorded in the study, but they do not provide a complete account of safety. Small event counts can be imprecise, and the record does not give event timing, duration, outcomes, participant-level overlap or detailed causality assessments. The figures should be read as safety reporting from this trial, not as a complete comparison of all harms or as a basis for individual treatment decisions.

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

The main result is a comparison of adverse-event-related drop-out after 6 weeks between two oxycodone/naloxone starting and titration schedules. The observed percentage was 40.91% for the 10/5mg starting schedule and 30.16% for the 5/2.5mg starting schedule. The recalculated risk difference was -0.107, with a 95% confidence interval from -0.224 to 0.009 and an unadjusted p-value of 0.072. The point estimate is lower for the group starting at 5/2.5mg, but uncertainty includes no difference.

This result does not establish that the schedules are equivalent. A non-significant p-value is not evidence that two approaches have identical effects, and the confidence interval does not exclude differences in either direction. Nor does the result establish that one schedule is preferable overall. The study’s primary measure is discontinuation due to an adverse event, not a complete assessment of symptom relief, functioning, quality of life or all safety outcomes.

The secondary results give additional, limited context. The registry reports mean changes in pain intensity and EQ-5D, with unadjusted comparisons whose confidence intervals include zero. These outcomes do not remove the uncertainty in the primary result. The registry record does not report numerical results for every further objective, including satisfaction and the 1-week drop-out outcome, in the available outcome summaries.

The conclusions that can be drawn are also bounded by reporting detail. The study was randomized but unmasked, and the record does not report the full analysis plan, original sample-size justification, detailed missing-data patterns or sensitivity analyses. The primary analysis used Last Observation Carried Forward, whose assumptions can matter when outcomes are missing. These limitations do not tell us the direction of any bias, but they make cautious interpretation appropriate.

Accordingly, the posted data describe a lower observed drop-out proportion in the group with the lower starting dose, alongside uncertainty that includes no difference. They do not prove a treatment effect, rule out clinically meaningful differences, or support a general claim about all patients with chronic pain. The result is specific to the registered schedules, outcome definition, follow-up period and analysis information reported for GLORY.

17. Why This Trial Matters Statistically

GLORY is statistically informative because it places a focused tolerability outcome beside a randomized comparison of two starting and titration schedules. The primary endpoint is directly tied to a practical study question: whether participants discontinued because of an adverse event during the first 6 weeks of treatment. Reporting the event proportions, counts and denominators makes the outcome interpretable as a group comparison rather than as a p-value alone.

The result also illustrates why point estimates and uncertainty need to be read together. The estimated risk difference is negative, but its confidence interval includes zero, and the unadjusted p-value is 0.072. A reader can see both the direction of the observed contrast and the imprecision around it. This is more informative than treating statistical significance as a simple verdict about whether a difference exists.

The study’s other outcomes demonstrate the value and difficulty of a broader outcome set. Pain intensity and EQ-5D describe dimensions distinct from discontinuation, but their estimates are also uncertain and the registry does not report a multiplicity plan. This makes the distinction between a prespecified primary question and secondary exploratory evidence especially important. The secondary outcomes can enrich interpretation without being treated as independent confirmation of the primary finding.

Finally, this record highlights the limits of registry-level statistical interpretation. It identifies randomization, masking, the primary analysis population and the imputation approach, but it does not report the complete analysis plan, original sample-size rationale or detailed missing-data information. Such details are needed to assess prespecification and robustness. Statistical interpretation therefore depends not only on the numerical estimate, but also on the design, outcome definition and completeness of analysis reporting.

18. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

The registry record leaves several trial-specific uncertainties. Although allocation is described as randomized, the method for generating and concealing the allocation sequence is not reported. The study is unmasked, but the record does not state whether outcome assessment was independently masked or how the open-label design was considered in analysis. These details matter because discontinuation and adverse-event attribution can involve participant or investigator judgment.

The schedules are described, but the registry does not report whether participants followed the planned titration steps, how dose changes were handled, or whether treatment exposure differed between groups. The primary endpoint’s detailed definition and adjudication process are also not reported. The study therefore allows comparison of the assigned schedules as described, but the record does not support a detailed analysis of adherence or the reasons underlying each discontinuation.

The primary analysis used an intent-to-treat population of 258 patients and Last Observation Carried Forward, but the registry does not report missingness by group, reasons for missing data or sensitivity analyses. EQ-5D summaries have smaller denominators than the primary outcome, and the reason is not stated. The registry also does not report the original sample-size calculation, full statistical analysis plan, covariate adjustment, multiplicity handling or reported inferential analyses for the secondary outcomes.

Safety reporting is limited in the registry summary. Serious-event counts and selected event terms are listed, but deaths are not reported, and details such as timing, relatedness and participant overlap are unavailable. These limitations do not demonstrate that the trial’s conduct or analyses were flawed; they define what can and cannot be evaluated from the registry record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: An Interventional Study to Compare the Efficacy and Tolerability With Targin® in Non-malignant Chronic Pain (GLORY) — NCT01811186.
• Registry record last updated 2017-03-10; status last verified 2017-01.
• Results first posted 2017-03-10.
• 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.

22. Record Summary

GLORY (NCT01811186) is a completed randomized, open-label, parallel-group phase 4 study sponsored by Mundipharma Korea Ltd. It compared two oxycodone/naloxone starting and titration schedules in non-malignant chronic pain. Enrollment is listed as 261, and the primary outcome analysis population is described as 258 patients using an intent-to-treat approach with Last Observation Carried Forward.

The primary outcome was adverse-event-related drop-out after 6 weeks. The reported rates were 40.91% for the group starting at 10/5mg twice daily and 30.16% for the group starting at 5/2.5mg twice daily. The recalculated unadjusted risk difference was -0.107, with a 95% confidence interval from -0.224 to 0.009 and p = 0.072. The interval includes no difference, leaving uncertainty about the comparative effect.

Pain intensity and EQ-5D change are also reported as secondary outcomes. Their unadjusted comparisons are imprecise, and the registry record does not report a full statistical analysis plan, the original sample-size rationale or detailed missing-data analyses.