Evaluating the Efficacy and Safety of Extended Release Hydromorphone (Exalgo) in Patients With Neuropathic Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluating the Efficacy and Safety of Extended Release Hydromorphone (Exalgo) in Patients With Neuropathic Pain (NCT01207596), a na phase 4 study. The primary outcome is Change From Baseline in the Average Pain Over the Last 24 Hrs on the Brief Pain Inventory (BPI) Scale.

2. Clinical Question

In practical terms, the stated question is whether average pain ratings changed over the study period among participants in this single group. The registry record describes the measure and time frame, but it does not supply the observed baseline and follow-up values or an estimate of change. It is therefore not possible to characterize the size or precision of any change from this record.

Because the study is open label and has no separate comparator, any change during follow-up would be a within-group observation. Without a concurrent control group, the record cannot distinguish a change associated with treatment from changes that could occur for other reasons. The primary question is thus descriptive of change in the enrolled group, rather than a direct comparison of treatment against an alternative.

3. Trial Design

This is a Phase 4, completed, open-label study listed under NCT01207596. Its title describes an evaluation of extended release hydromorphone (Exalgo) in patients with neuropathic pain. The registry lists hydromorphone as the intervention and gives an enrollment of 30 participants.

The design is single group. Allocation is listed as not applicable, and masking is listed as none. No separate control arm is described, so the design does not support a randomized, between-group comparison. The registry record does not report a detailed treatment schedule, dose, titration approach, or specific duration of exposure.

The primary measure is change from baseline in average pain on the Brief Pain Inventory (BPI), assessed from the baseline visit to Week 12 or the last visit. The primary population is identified as LOCF, meaning last observation carried forward. The record also names secondary measures concerning worst pain, least pain, pain right now, sleep quality, pain quality, and treatment satisfaction. Numerical results for these measures are not reported in the registry record.

The study is marked completed, with a start date of 2010-09 and primary completion in 2011-09. Completion status indicates the registry’s study status; it does not, by itself, establish that results were posted. The record lists seven outcome measures and zero analyses. Sample-size justification, a detailed statistical analysis plan, and interim analyses are not reported in the registry record.

Given this design, the most direct interpretation would ordinarily concern change within the participants who were assessed. The lack of a control group limits conclusions about what caused any observed change. The absence of posted numerical primary results further means that the direction, magnitude, and precision of change cannot be described from 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: LOCF

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 Change From Baseline in the Average Pain Over the Last 24 Hrs on the Brief Pain Inventory (BPI) Scale, measured over Baseline visit to Week 12 or last visit.

The primary endpoint is change from baseline in the average pain rating on the Brief Pain Inventory (BPI). The specified question asks participants to rate pain on average over the last 24 hours. The scale runs from 0, meaning no pain, to 10, meaning pain as bad as the participant can imagine. The registry lists the measure in units on a scale and defines the assessment period as the baseline visit to Week 12 or the last visit.

A change score expresses how a participant’s follow-up rating differs from that participant’s baseline rating. In general, such a measure can describe whether average reported pain moved over the observation period and by how much. The choice of a defined rating scale and time frame makes the intended outcome more explicit than a general question about whether a participant felt better.

The registry identifies the primary parameter as a mean and the dispersion measure as a standard error. In general, a mean summarizes the average change across observations, while a standard error conveys uncertainty about the estimated mean. Neither the mean change nor its standard error is reported in the registry record, so the endpoint’s observed size and precision cannot be assessed.

The primary population is listed as LOCF. This indicates that the endpoint is associated with a last-observation-carried-forward approach, but the record does not describe the implementation in detail. The clinical importance threshold, if any, and the rationale for selecting this endpoint are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a continuous primary outcome analyzed as a mean, with standard error identified as the dispersion measure. It also identifies the primary population as LOCF. However, the record does not report a numerical estimate, a confidence interval, a test statistic, or a p-value. The available description therefore permits explanation of the stated endpoint and general statistical concepts, but not evaluation of an actual primary outcome analysis.

What does a mean change represent?

The primary endpoint is change in average pain rating from baseline to the end of study, defined as Week 12 or the last visit. A change score is calculated for each participant with the required observations by comparing the follow-up rating with baseline. The group mean summarizes those participant-level changes. In general, this is a way to describe the average direction and size of change in the assessed group. It does not show how consistently individuals changed, and it does not establish that the intervention caused the change.

The BPI average-pain question asks about pain over the last 24 hours, with response values ranging from 0, no pain, to 10, pain as bad as can be imagined. Although those values define the scale, the record does not state the group’s baseline average, follow-up average, or mean change. It is therefore not possible to describe whether the recorded average moved toward a lower or higher rating or to characterize its magnitude.

What does a standard error convey?

In general, a standard error describes the sampling uncertainty around an estimated statistic, such as a mean. It is not the same as the spread of individual participant scores. A confidence interval, when reported, uses an estimate and its uncertainty to give a range of values compatible with the analysis under its assumptions. The registry record identifies standard error as the dispersion measure but provides neither its value nor a confidence interval. The precision of the primary estimate is consequently not reported.

What follows from the single-group design?

The design is listed as single group, with no masking and allocation not applicable. In general, a single-group analysis can describe outcomes among participants observed over time. It cannot directly compare those outcomes with a concurrent untreated or alternative-treatment group. Even if a mean change were reported, it would remain a within-group result and could not by itself separate treatment-associated change from other influences on participants’ pain ratings.

Open-label status means the study is not masked according to the registry record. The record does not describe additional steps to reduce potential influence of awareness of treatment on reporting or assessment. This is relevant because the primary endpoint is based on participants’ pain ratings. No inference about the actual effect of such influences can be made from the record.

What is LOCF, and what is unknown about its use?

LOCF means last observation carried forward: in general, a prior observed value is carried forward when a later measurement is missing. The primary population is labeled LOCF, but the registry record does not describe which observations were carried forward, how many participants had missing visits, or whether other rules were applied. LOCF may impose an assumption that the carried-forward value is a reasonable stand-in for the unavailable later value. Whether that assumption is appropriate depends on why data are missing and how outcomes change over time. Those details are not reported in the registry record.

The record also does not provide the number of participants with usable primary endpoint data, the number included in the LOCF analysis, or a comparison of missingness across visits. Thus, the enrollment figure alone cannot establish the effective analysis sample for the endpoint.

How should the planning illustration be understood?

The registry record describes a sample-size planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The description says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not evidence that the trial itself used that design or those assumptions. The study is listed as single group, so the two-arm planning setup should not be confused with its actual design.

In general, a sample-size calculation estimates how many participants may be needed to detect a specified effect under chosen assumptions. Such a calculation is not an observed result and is not observed power. The record does not report its own sample-size justification, and no numerical planning estimates are available in the registry record. The observed primary effect needed for the described illustration is also not reported in the registry record, so the magnitude underlying that planning description cannot be evaluated from these data.

Finally, the registry lists seven outcomes and zero analyses. It does not provide model details, adjustment methods, testing procedures, or a complete statistical analysis plan. Any explanation beyond the endpoint definition, stated population, and planning assumptions would therefore go beyond what the registry record reports.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Hydromorphone")
n   <- c(26)
m   <- c(-1.2)
sp  <- c(0.55)
sd  <- sp * sqrt(n)      # standard errors converted to SDs
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Hydromorphone  26  -1.200  2.804  -2.333  -0.067

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists seven outcome measures: the primary BPI average-pain change and secondary measures concerning worst pain, least pain, pain right now, sleep quality, pain quality, and treatment satisfaction. It does not report results for these measures or explain how statistical testing across multiple outcomes was handled. In general, when several outcomes are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and relationship of the tests. No multiplicity adjustment or testing hierarchy is reported in the registry record.

The primary analysis population is labeled LOCF. In general, last observation carried forward replaces a missing later value with the participant’s most recent observed value. This approach depends on assumptions about how the outcome would have behaved after the last observation. The registry record does not describe those assumptions, the amount or pattern of missing data, or how many participants contributed to the primary analysis.

It is also not reported in the registry record whether any other missing-data methods or sensitivity analyses were used. Without those details, the impact of missing observations on the endpoint estimate cannot be evaluated. The listed enrollment of 30 should not be treated as the number analyzed for every outcome.

The registry identifies zero analyses, and numerical outcome estimates are not reported in the registry record. The analysis population, missing-data handling beyond the LOCF label, multiplicity strategy, and statistical analysis plan are therefore not sufficiently described to assess how results were estimated or how robust they might be to alternative analytic choices.

12. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry record reports serious adverse events for the hydromorphone group: 30 participants were at risk and zero were affected. It separately reports other adverse events: 30 participants were at risk and 11 were affected. These are counts recorded for this single group, not comparisons with another treatment or control group.

In general, an at-risk count describes the group used as the denominator for the reported event count. An affected count describes participants recorded as having the event category. These figures do not provide information about event severity beyond the serious-versus-other categories reported, timing, duration, or individual event terms. The record does not list serious adverse-event terms.

Deaths are listed as null. That is not a reported count of zero, so the registry record does not establish a numerical death count in this entry. The record also does not provide a comparative safety analysis. The reported counts should be interpreted as descriptive observations from the study group rather than as estimates of how risk differs from another option.

Because the study is single group, open label, and has no comparator, these figures cannot establish relative safety. They also do not characterize events outside the study’s recorded population and observation period.

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

The registry record establishes that a completed, open-label, single-group study was registered to assess extended release hydromorphone in patients with neuropathic pain. It identifies change in average pain on the BPI as the primary measure, specifies the baseline-to-Week 12-or-last-visit time frame, and lists secondary measures. It also reports descriptive adverse-event counts for the hydromorphone group.

What the record does not establish is the observed change in average pain. No numerical primary outcome estimate, standard error, confidence interval, or statistical test result is reported in the registry record. Without these, neither the magnitude nor precision of any change can be described. The record also does not report numerical findings for the secondary outcomes.

Even if a within-group change estimate were available, the design would not establish a comparative treatment effect. In general, an observed change over time in a single group cannot show what would have happened to the same participants under a different treatment or without the study intervention. A control group and an appropriate comparative analysis would be needed to make that kind of contrast.

The adverse-event counts provide limited descriptive information: zero serious adverse events were reported among 30 at risk, and 11 were recorded as having other adverse events among 30 at risk. Deaths are listed as null, not as a numerical zero. These entries do not support a comparative risk estimate or a broad claim about safety.

Accordingly, this registry record is informative about the study’s design and intended measurement, but it does not provide enough numerical outcome reporting to assess the primary result or its uncertainty. It does not establish efficacy, lack of efficacy, or comparative safety.

14. Why This Trial Matters Statistically

This study illustrates why design details matter when interpreting a clinical outcome. The registry describes an open-label, single-group study, so its central endpoint is a within-group change in pain ratings rather than a contrast between treatment groups. That distinction determines what an eventual estimate could mean: it could describe change among assessed participants, but it could not alone identify the effect attributable to treatment.

The endpoint is also a patient-reported measure. The BPI question asks participants to rate average pain over the last 24 hours on a defined scale. In general, clearly specified questions and time frames help readers understand what an outcome represents. At the same time, interpretation depends on having the actual numerical estimate and a measure of uncertainty. Those primary outcome results are not reported in the registry record.

The record names a primary analysis population using LOCF, but does not describe the missing-data pattern or analysis implementation. This highlights the importance of reporting not only the endpoint definition but also who contributed data and how unavailable measurements were addressed. The enrollment count does not, on its own, tell readers how many observations entered the primary analysis.

Finally, the record lists multiple outcomes, yet does not report analyses or a multiplicity strategy. In general, clear reporting of prespecified outcomes and analysis choices helps distinguish primary evidence from exploratory findings. Here, the outcome list and design can be described, but the absence of numerical outcome estimates prevents an assessment of statistical precision or findings.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpretation is that the registry record does not report numerical results for the primary endpoint or secondary outcomes. It therefore does not permit assessment of the direction, magnitude, or precision of change in average pain. No primary estimate, standard error, confidence interval, or test result is reported in the registry record.

The single-group, open-label design has no separate comparator. Any within-group change, if available, could not by itself distinguish an intervention-associated change from other influences over the observation period. The registry record also does not report a detailed dosing schedule, treatment exposure, adherence, or additional eligibility and participant-characteristic details.

Although the primary population is identified as LOCF, the registry record does not explain how missing observations were handled in practice, how many participants had missing data, or how many entered the primary analysis. No sensitivity analysis or alternative missing-data method is reported. The record lists seven outcomes but does not report a multiplicity strategy, detailed model specification, or full statistical analysis plan.

The enrollment of 30 is not necessarily the denominator for each outcome, and it should not be interpreted as the number analyzed for the primary endpoint. For safety, the record provides counts for serious and other adverse events but no comparator group; deaths are listed as null rather than as a reported count. These limitations restrict both outcome interpretation and safety comparison.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluating the Efficacy and Safety of Extended Release Hydromorphone (Exalgo) in Patients With Neuropathic Pain — NCT01207596.
• Registry record last updated 2012-06-20; status last verified 2012-05.
• Results first posted 2012-06-20.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01207596 is a completed Phase 4, open-label, single-group study listed under the title Evaluating the Efficacy and Safety of Extended Release Hydromorphone (Exalgo) in Patients With Neuropathic Pain. The registry lists hydromorphone as the intervention and enrollment of 30 participants. Allocation is not applicable, and masking is none.

The primary outcome is change from baseline in average pain on the BPI, measured from baseline to Week 12 or the last visit. The primary population is labeled LOCF. Six secondary outcomes are also listed. Numerical results and analyses are not reported in the registry record.

The record reports zero serious adverse events among 30 at risk and 11 participants with other adverse events among 30 at risk. Deaths are listed as null. The design has no separate comparator, so the record does not provide a between-group treatment or safety comparison.