A Study of the Safety and Efficacy of AGN-214868 in Patients With Postherpetic Neuralgia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Safety and Efficacy of AGN-214868 in Patients With Postherpetic Neuralgia (NCT01129531), a randomized phase 2 study. The primary outcome is Change From Baseline in the Average Pain Intensity Score at Week 12.

2. Clinical Question

3. Trial Design

This was a randomized, double-masked, parallel Phase 2 study of AGN-214868 in participants with postherpetic neuralgia. The registry lists Allergan as the sponsor and records the study as completed. The recorded study start was 2010-06, and primary completion was 2011-10. Enrollment is listed as 294.

The intervention was AGN-214868 injected into areas of postherpetic neuralgia pain. Two dose groups are described: 3.25 μg and 16.25 μg per treatment. The comparator was placebo to AGN-214868, also injected into areas of pain. The record does not report how often treatment was administered, how long treatment continued, or additional details about the injection procedure.

Randomization means that assignment to the study groups was intended to be determined by chance. In general, this can help balance measured and unmeasured participant characteristics across groups, although chance imbalances can remain. Double masking means the study used masking for two parties, but the registry record does not identify which parties were masked or describe how masking was maintained. A parallel design assigns participants to a group for comparison rather than describing a crossover between interventions.

The primary outcome was change from baseline in average pain intensity at Week 12. The primary-outcome population was defined as randomized participants who received treatment and had at least one post-baseline pain-intensity score. The registry record does not report the randomization procedure, allocation concealment, treatment schedule, or statistical plan. It also does not provide the number assigned to each group in the trial-design information.

4. Participant Flow and Accounting

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

Before assignment: There were two Treatment Cycles in this study 12 weeks apart. In Treatment Cycle 1 participants were randomized to AGN-214868 3.25 μg, AGN-214868 16.25 μg or Placebo. In Treatment Cycle 2 participants were re-randomized to AGN-214868 3.25 μg, AGN-214868 16.25 μg or Placebo.

Treatment Cycle 1

Treatment Cycle 2

Analysis population for the primary outcome, as defined in the registry: Modified intent to treat population included all randomized participants who received treatment and had at least 1 post-baseline pain intensity score.

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 Intensity Score at Week 12, measured over Baseline, Week 12.

The primary endpoint was change from baseline in average pain intensity at Week 12. Participants rated the severity of their daily pain over the previous 7 days using a 10 point scale, from 0, no pain, to 10, pain as bad as you can imagine. A negative change from baseline indicated improvement. The scale therefore represents a patient-reported measure of pain intensity, and the change score describes how the rating at follow-up differs from the baseline rating.

In general, a continuous pain score can capture degrees of symptom severity rather than sorting participants only into categories such as improved or not improved. A change-from-baseline measure also focuses on movement over time, while interpretation depends on how the change is compared between randomized groups. For a treatment comparison, a group-level estimate and its uncertainty would be needed to understand the size and precision of any difference.

The registry record does not report the primary-outcome group estimates, a between-group contrast, a confidence interval, or a p-value. Its note indicates that the primary outcome has several categories or time points and was not reduced to one comparison. Thus the endpoint definition is available, but a numerical result for the Week 12 comparison is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a continuous primary outcome: change from baseline in average pain-intensity score at Week 12. The endpoint is summarized as a mean, with standard deviation identified as the dispersion measure. These descriptors identify a type of summary, not the actual observed mean or standard deviation; those values are not reported in the registry record.

What does a mean change represent?

In general, the mean is the arithmetic average of individual measurements. For a change score, each participant’s follow-up score is considered relative to that participant’s baseline score, and a group mean summarizes those changes. A mean can provide a useful description of the group’s average trajectory, but it does not show how individual responses were distributed. The standard deviation describes variation among observations around the mean; it is not the uncertainty of the estimated mean and is not a confidence interval.

The registry states that negative change indicates improvement on the pain scale. That direction helps interpret a group’s change, but a comparison between randomized groups requires a contrast between their outcome summaries. A favorable direction in one group alone is not enough to establish a difference between groups. The group means, their standard deviations, and a between-group estimate are not reported in the registry record.

What would a confidence interval tell a reader?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical method. For a group contrast, its width reflects precision: a narrower interval indicates a more precise estimate under the method’s assumptions, while a wider interval indicates greater uncertainty. The interval’s location also matters, because it shows which magnitudes and directions are compatible with the analysis. No confidence interval for the primary comparison is reported in the registry record.

A p-value, in general, assesses how compatible the observed data are with a specified null hypothesis under the analysis assumptions. It does not measure the probability that the null hypothesis is true, and it does not communicate the size of an effect. A p-value should be read alongside an effect estimate and its uncertainty. No primary-outcome p-value is reported in the registry record.

What can the design contribute?

Random allocation can support a comparison of groups because, in general, it reduces systematic differences in treatment assignment. Masking can reduce the influence of knowledge about assignment on some aspects of care, reporting, or assessment. These are general design benefits, not confirmation that bias was eliminated in this study. The registry records randomization and double masking but does not report the allocation procedure, who was masked, or how masking was maintained.

The study is described as parallel, so the groups are presented as concurrent treatment groups. The registry does not give further details of the statistical model used for the primary outcome. In particular, it does not report whether the analysis adjusted for baseline score, included other covariates, accounted for repeated measurements, or used any particular variance estimator. These details can affect both the estimated contrast and its uncertainty, so an analysis cannot be reconstructed from the endpoint definition alone.

How should planning illustrations be understood?

In general, a sample-size calculation for planning uses assumptions about the effect to detect, the significance level, allocation, and statistical model. The planning description associated with this study specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes the target effect as a stated fraction of the observed effect. These are planning assumptions, not evidence about the trial’s observed results or proof that the study had a particular probability of detecting an effect.

The description says that sample-size illustrations for non-time-to-event outcomes are expressed as participants per arm; time-to-event illustrations use total events. This primary outcome is continuous, not time-to-event. Any such planning illustration should be understood as a hypothetical design calculation rather than an observed sample size or an observed-power calculation. The registry record does not report the trial’s own sample-size justification or a statistical plan establishing that these planning assumptions were used to design the trial.

Over-dispersion is a general concern when variation is greater than a model assumes. If a method underestimates variability, its uncertainty estimates may be too small; methods that account for extra variation can produce more appropriate uncertainty. The registry record does not state that over-dispersion was assessed or that a particular model requiring such an adjustment was used. It would therefore be inappropriate to attribute a specific method or correction to this study.

Overall, the methods information identifies an endpoint scale, a mean summary, a dispersion measure, the primary population definition, and general planning assumptions. It does not report the fitted analysis, numerical estimates, confidence intervals, p-values, or model diagnostics. Those omissions limit statistical interpretation and prevent an independent reconstruction of the primary comparison.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and three named secondary outcomes: change from baseline in area of spontaneous pain, change from baseline in area of allodynia, and change from baseline in evoked pain score in the area of allodynia. The outcome information includes four outcome measures. The record also notes that the primary outcome has several categories or time points and was not reduced to one comparison. This makes it important to know which comparisons were designated as primary and how multiple tests or time points were handled. A multiplicity strategy is not reported in the registry record.

In general, when many hypotheses are tested, the chance of at least one apparently unusual result can increase. Prespecified testing sequences, adjusted significance thresholds, or other methods can address this issue, but none should be assumed without documentation. The registry record lists zero analyses in the available outcome information, so it does not provide a test-by-test account or results from which to judge the impact of multiple comparisons.

The primary analysis population is defined as randomized participants who received treatment and had at least one post-baseline pain-intensity score. This definition clarifies who was included in the stated population, but it does not describe how missing outcome measurements were handled. Missing-data methods, the amount of missingness, reasons for missing measurements, and sensitivity analyses are not reported in the registry record.

In general, missing data can affect a treatment comparison when the chance of an outcome being unavailable is related to participant characteristics or outcomes. Methods for handling missingness rely on assumptions, and sensitivity analyses can explore how conclusions depend on them. The record does not identify an imputation method, a repeated-measures method, or another approach. It also does not report whether participants without post-baseline scores were excluded from the primary analysis beyond the stated population definition.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: basal cell carcinoma (2.1%), myocardial infarction (1.3%), gastroduodenitis (1.3%), dehydration (1.3%), depression (1.3%).

The registry reports serious and other adverse-event figures separately for treatment-cycle groups. For Cycle 1, the AGN-214868 3.25 μg group lists 1 serious event among 84 at risk and 1 other adverse event among 84 at risk. The AGN-214868 16.25 μg group lists 2 serious events among 83 at risk and 1 other adverse event among 83 at risk. The placebo group lists 1 serious event among 125 at risk and 2 other adverse events among 125 at risk.

For Cycle 2, the AGN-214868 3.25 μg group lists 5 serious events among 94 at risk and 6 other adverse events among 94 at risk. The AGN-214868 16.25 μg group lists 5 serious events among 95 at risk and 1 other adverse event among 95 at risk. The placebo group lists 3 serious events among 79 at risk and 3 other adverse events among 79 at risk. These are registry-reported figures by cycle; they should not be combined across cycles or interpreted as a unique-participant count.

The record lists serious-event terms with percentages, including Basal cell carcinoma at 2.1%, Myocardial infarction at 1.3%, Gastroduodenitis at 1.3%, Dehydration at 1.3%, Depression at 1.3%, and Chest pain at 1.2%. The denominators and detailed basis for these term percentages are not reported in the registry record. Death counts are not reported in the registry record. These summaries do not establish causality or provide a complete account of event timing, duration, or severity.

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

The record establishes that this was a randomized, double-masked, parallel Phase 2 study comparing two AGN-214868 dose groups with placebo in participants with postherpetic neuralgia. It also defines the primary outcome as change from baseline in average pain intensity at Week 12 and explains how to interpret the direction of the score. These registry entries describe the design and question, not the study’s primary result.

The numerical primary-outcome estimates, between-group comparison, confidence interval, and p-value are not reported in the registry record. Therefore, the posted information does not show how much pain intensity changed in each group, how the groups compared, or how precisely any difference was estimated. The absence of these results cannot be treated as evidence of no difference, nor as evidence of benefit. It leaves the primary comparison unresolved in the record.

In general, a treatment comparison is most informative when it includes an estimated difference and an uncertainty measure, interpreted in light of the prespecified analysis. Statistical evidence and clinical importance are related but distinct: an estimate may be statistically precise without establishing how meaningful its size is, and an imprecise estimate may leave a range of possible effects. No numerical estimate is available to make either assessment.

The registry also identifies secondary pain outcomes and adverse-event summaries. Their listing does not substitute for the missing primary-outcome comparison. Safety figures are organized by treatment cycle and include reported counts of serious and other adverse events; they should be read in that structure rather than combined into a participant total. The record does not report enough detail to infer the cause of individual events or to make a comprehensive safety comparison.

Thus, the statistical meaning of the posted record is mainly descriptive: it specifies who the primary analysis was intended to include, what was measured, and when. It does not provide the outcome estimates needed to determine the direction, magnitude, or precision of the randomized-group comparison.

13. Why This Trial Matters Statistically

This study illustrates why a clearly defined endpoint and a reported treatment contrast are both necessary for statistical interpretation. The registry provides a specific pain-intensity scale, a baseline-to-Week-12 time frame, and the direction that represents improvement. These details make the outcome definition understandable and reproducible in principle. However, without group estimates and an uncertainty measure, readers cannot assess the actual contrast that the randomized design was intended to examine.

The study also highlights the importance of a transparent analysis population. The primary population is defined as randomized participants who received treatment and had at least one post-baseline pain-intensity score. That definition is useful, but it does not answer how missing measurements were handled or whether other populations were analyzed. Clear reporting of exclusions and missing-data methods would help readers judge the assumptions behind an estimate.

Multiple outcomes and time points add another statistical consideration. The registry identifies secondary outcomes and notes that the primary outcome includes several categories or time points. Without a reported multiplicity plan and analysis results, it is not possible to distinguish confirmatory comparisons from exploratory ones or assess how testing choices were handled. These are general concerns in trials with multiple endpoints, rather than claims about what occurred in this study.

Finally, safety reporting by cycle illustrates why counts need context. Cycle-specific figures and denominators should be interpreted as reported, not silently merged into a single count. The record’s safety summaries and endpoint definitions contribute useful design information, but they do not replace transparent estimates, uncertainty, and analysis methods for the main randomized comparison.

14. Limitations

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

The main limitation for statistical interpretation is that the registry record does not report numerical results for the primary endpoint. There are no group means, standard deviations, between-group estimate, confidence interval, or p-value in the available record. The note that the primary outcome has several categories or time points and was not reduced to one comparison further limits the ability to identify a single primary contrast.

The analysis details are also sparse. Although the primary population is defined, the statistical model, baseline adjustment, treatment of repeated measurements, missing-data method, and sensitivity analyses are not reported in the registry record. The record does not state how randomization was carried out, which parties were masked, or how allocation concealment and masking were maintained. No sample-size justification or trial-specific statistical plan is reported.

The safety information is reported by treatment cycle, and the term percentages are listed without their denominators or further methodological context. Death counts are not reported in the registry record. The registry entries do not explain whether events were judged related to treatment, how long participants were followed for safety, or how event summaries were formed across cycles. These gaps restrict comparison and causal interpretation.

These limitations concern what can be concluded from the registry record; they do not establish that the trial lacked additional analyses or documentation elsewhere. They mean that a reader relying on this record cannot independently evaluate the magnitude or precision of the primary comparison, the handling of missing outcomes, or the statistical treatment of multiple endpoints.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of the Safety and Efficacy of AGN-214868 in Patients With Postherpetic Neuralgia — NCT01129531.
• Registry record last updated 2013-11-15; status last verified 2013-09.
• Results first posted 2013-11-15.
• 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.

18. Record Summary

The registry record describes a completed randomized, double-masked, parallel Phase 2 study of AGN-214868 for postherpetic neuralgia. Enrollment is listed as 294, with a study start of 2010-06 and primary completion of 2011-10. The intervention groups received AGN-214868 at total doses of 3.25 μg or 16.25 μg per treatment, and the comparator was placebo to AGN-214868.

The primary outcome was change from baseline in average pain intensity at Week 12, assessed on a 10 point scale. The primary population included randomized participants who received treatment and had at least one post-baseline score. Numerical primary-outcome results and analysis details are not reported in the registry record. Safety figures are reported by treatment cycle, and three secondary pain outcomes are listed.