Pain Expectations in Subjects With Osteoarthritis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pain Expectations in Subjects With Osteoarthritis (NCT02155257), a randomized phase 4 study. The primary outcome is Resting Pupil Diameter.

2. Clinical Question

The study is framed as a feasibility investigation: its stated purpose is to test whether researchers can alter pain expectations. That aim differs from a definitive assessment of clinical benefit. The primary endpoint is a physiological measurement, rather than a direct report of pain expectations. Thermal heat responses are also mentioned in the brief summary, but the registry record does not identify them as the primary endpoint or provide their results.

The record identifies osteoarthritis as the condition and describes participants with knee or hip osteoarthritis as well as healthy subjects for comparison. It does not report the numbers in those subgroups, their baseline characteristics, or how the healthy comparison group was incorporated into the randomized treatment groups. Accordingly, the central question that can be described from the record is whether resting pupil diameter was measured before and after the assigned dose. Whether the treatment groups differed, and how any difference related to pain expectations, is not reported in the registry record.

3. Trial Design

This was a Phase 4, randomized, triple-masked, parallel-group study sponsored by Wake Forest University Health Sciences. The registry lists enrollment of 30. Its listed interventions were modafinil, gabapentin, and placebo. The arm descriptions specify one-time oral administration: modafinil 200 mg, gabapentin 900 mg, or placebo. The safety record lists 10 participants at risk in each intervention group.

The parallel design means participants were assigned to a group and the groups received different interventions, rather than each participant receiving every intervention in sequence. Random allocation is intended, in general, to make treatment groups comparable on average at assignment; it does not guarantee identical groups, especially in a feasibility study with limited enrollment. Triple masking indicates that the registry classifies the study as triple-masked, but it does not identify which roles were masked or describe how masking was maintained. Those details are not reported in the registry record.

The study began in 2014-07, reached primary completion in 2017-10, and is listed as completed. The registry record does not report the recruitment process, the allocation procedure, treatment adherence, or the number of participants who completed each assessment. It also does not report a protocol rationale for the enrollment target or details of any planned interim analyses.

The primary outcome is resting pupil diameter in millimeters, measured at baseline and 2 hours after dosing. The record lists 3 outcome measures and one analysis, but does not give enough information to determine the full analysis specification or to identify a particular treatment contrast as primary. The posted information therefore describes the treatment groups, timing, and outcome concept, but not the numerical comparison results.

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

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 Resting Pupil Diameter, measured over Baseline and 2 hours.

Resting pupil diameter is a continuous measurement recorded in millimeters. The registry describes using an infrared camera to measure pupil diameter at baseline and repeating the measurement 2 hours after dosing. The primary outcome is listed as a mean with standard deviation as its dispersion measure.

A physiological measurement can be useful in a study of pain expectations because it gives researchers an observable response to examine alongside other measures. The brief summary links the study to pupil size and responses to thermal heat, and states that the research aims to test whether pain expectations can be altered. The registry record does not explain the biological interpretation of pupil diameter in this study, establish that it is a validated measure of pain expectation, or report how it relates to thermal heat responses.

Repeated measurement at baseline and after dosing can describe change over time, while comparisons among randomized groups can assess whether the observed patterns differ by assigned intervention. The registry record does not report the group means, standard deviations, changes from baseline, or a treatment comparison. It is therefore not possible to characterize the size, direction, or precision of any observed difference from the posted primary outcome information. The stated timing and measurement method identify what investigators intended to assess, not what the results were.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a mean and standard deviation describe?

The primary outcome is specified as a mean with standard deviation. In general, the mean summarizes the center of a set of continuous measurements, while the standard deviation describes how spread out individual measurements are around that center. They answer different questions: a group mean describes its average pupil diameter, and a standard deviation describes variability among measurements in that group. Neither quantity alone gives the uncertainty in a comparison between groups.

For this outcome, the registry identifies millimeters as the unit and names baseline and 2 hours after dosing as the measurement times. However, the group means and standard deviations are not reported in the registry record. It is therefore not possible to describe average pupil diameter, variation, or the amount of change from baseline based on the posted results.

How would a treatment comparison be interpreted?

In general, a treatment comparison estimates how an outcome differs between assigned groups. For a continuous endpoint, a difference in means is one common way to express a comparison, but the registry record does not specify the contrast or report an estimate. A comparison could focus on measurements at a particular time, change from baseline, or another prespecified summary. Which approach was used is not reported in the registry record, so no particular method should be assumed.

A confidence interval describes uncertainty around an estimated effect under the assumptions of the analysis. It helps readers consider both the range of effects reasonably compatible with the data and the precision of the estimate. A p-value, in general, measures how compatible the observed data are with a specified null model, given the model’s assumptions. Neither quantity conveys the full importance or meaning of an effect by itself. The registry record does not report a confidence interval or p-value for resting pupil diameter.

Why does variability matter?

Continuous outcomes can vary between people, and measurements can also vary within a person over time. When variability is large relative to a treatment contrast, it can be difficult to estimate that contrast precisely. General statistical methods may account for such variability through the model and its standard errors. The registry record does not report the observed variability, model, or standard errors, so the precision of the primary outcome comparison cannot be assessed.

Over-dispersion is a general concern when the variability in data exceeds what a chosen statistical model expects. It can make standard errors too small if the model is not suitable. This study’s primary outcome is continuous, and the record identifies a mean and standard deviation, but it does not report an over-dispersion assessment or a model for the outcome. There is no basis in the registry record to say whether this issue arose or how it was addressed.

What do randomization and masking contribute?

Random allocation is intended to reduce systematic differences in the assignment of participants to treatment groups. In general, it helps support a fair comparison, but it cannot ensure that groups are identical, and it does not resolve missing outcome data or imprecision. Masking can reduce the influence of expectations on care, measurement, or reporting, depending on which people are masked and how the procedures are implemented. The record classifies the study as randomized and triple-masked but does not describe the randomization procedure, masking roles, or implementation.

The parallel design assigns participants to a group rather than comparing multiple study treatments within the same participant. The reported treatment groups are modafinil, gabapentin, and placebo. Although the record lists those groups, it does not report which pairwise or overall comparison generated the single listed analysis. No specific contrast should be inferred from the design description alone.

How should the planning illustration be understood?

The registry’s planning statement describes a hypothetical sample-size calculation using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It says that the effect to detect is expressed as a stated fraction of the observed effect. This is a planning illustration based on an observed effect, not evidence that the study was designed with that target or that its results have a particular probability of being statistically significant. The registry record does not report numerical planning estimates or a sample-size justification for the trial’s original design.

In general, a sample-size calculation asks how many participants would be needed under specified assumptions to detect an effect with a chosen level of power. A planning calculation is conditional on its assumed effect, variability, allocation, and analysis method. It is not “observed power,” and it does not substitute for an effect estimate with an uncertainty interval. The stated calculation concerns equal allocation between two arms, whereas the trial lists three intervention groups. The registry record does not explain how the planning illustration relates to the three-group design.

Because no primary outcome estimates or analysis details are reported, statistical interpretation must remain descriptive. The general concepts above explain how such data could be evaluated; they do not establish what this study found.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and one analysis. The primary endpoint is measured at baseline and 2 hours after dosing, and the record’s note indicates that the primary outcome has several categories or time points and was not reduced to one comparison. This means the posted information does not define a single numerical primary contrast for interpretation. The registry record does not report whether the analyses were adjusted for multiple comparisons, how outcomes or time points were prioritized, or whether any multiplicity procedure was planned.

In general, multiplicity arises when several outcomes, time points, groups, or contrasts are examined. Without a prespecified approach, repeated testing can increase the chance of highlighting a result that appears noteworthy by chance. Adjustment methods can address some forms of this issue, but the appropriate method depends on the intended comparisons and analysis plan. No multiplicity method is reported in the registry record, so no claim about adjustment or its absence in the actual analysis is warranted.

Missing-data handling is also not reported in the registry record. The posted information does not say whether every randomized participant contributed baseline and follow-up measurements, how incomplete measurements were handled, or whether any imputation or sensitivity analysis was used. It does not report the analysis population, such as whether analyses followed assigned treatment or included only participants with available measurements. These details matter because the analyzed participants and assumptions about missing measurements can affect estimates and uncertainty.

The registry record does not report the statistical analysis plan, the model for the primary endpoint, covariate adjustment, or interim analyses. These omissions limit reproducibility and prevent a detailed assessment of how the reported design would translate into an analysis. They do not establish that any particular procedure was or was not used.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

The registry lists 10 participants at risk in each of the modafinil, placebo, and gabapentin groups. It records zero serious adverse events in each group and zero deaths in each group. It also records zero other adverse events in each group. These are the counts posted for the study; the registry record does not provide event descriptions or additional safety analyses.

A zero count means that no event in that category was recorded among the participants included in the listed group. It does not demonstrate that the risk is zero, and it does not establish that the groups have equivalent safety. With a limited number of participants, uncommon events may not be observed. In general, event counts are more informative when considered alongside the number of participants monitored, the duration of monitoring, definitions of events, and completeness of reporting. The registry record does not report the observation duration for safety events or further details on their ascertainment.

The counts should therefore be read as a concise description of the registry’s recorded serious events, not as a definitive comparison of safety between interventions. No inference about relative risk or statistical precision can be made from the posted counts alone.

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

The registry record establishes that a completed randomized, triple-masked, parallel-group study evaluated a one-time oral dose of modafinil 200 mg, gabapentin 900 mg, or placebo. It identifies resting pupil diameter as the primary outcome and specifies measurements at baseline and 2 hours after dosing. It also states that the study aimed to investigate whether pain expectations could be altered and mentions thermal heat responses.

These design details do not reveal the outcome. The primary endpoint values, their variability, and comparisons among groups are not reported in the registry record. Consequently, the posted information does not show whether resting pupil diameter increased, decreased, or remained similar, or whether the groups differed. It also does not show whether pain expectations or thermal heat responses changed. No statistical conclusion about those questions can be drawn from the record’s design description.

The study is described as a feasibility study, and its enrollment is 30. Feasibility aims and a limited enrollment can be relevant when interpreting a study’s scope, but the record does not report its feasibility criteria or outcomes. The registry also does not give a sample-size justification for the original study. The planning statement is an illustration based on an observed effect, not a report of the trial’s observed power or a substitute for outcome estimates.

Zero serious adverse events are recorded for each group, with 10 participants at risk in each. Those counts describe what was posted, but they do not establish absence of risk or comparative safety. More generally, the lack of numerical outcome results is not evidence that there was no effect; it means the registry record does not permit the effect to be characterized.

The appropriate boundary is therefore clear: the record supports describing the study’s design, groups, measurement schedule, and recorded event counts. It does not support claims about treatment effects, their size, their direction, or their precision.

13. Why This Trial Matters Statistically

This study is statistically notable for the distinction between a clearly described research question and an outcome result that is not reported in the registry record. The design identifies randomized assignment to three interventions and names a continuous primary endpoint, but without its estimates and uncertainty, readers cannot evaluate the central comparison. A trial’s design is essential context; it is not a substitute for results.

The feasibility framing also makes it important to separate planning from estimation. A feasibility study may be organized around whether research procedures can be carried out, while a treatment-effect estimate addresses a different question. The registry record states that this research tests whether pain expectations can be altered, but does not report feasibility criteria or findings. Nor does it report a justification for enrollment of 30. Readers should not treat the planning illustration as the original design rationale.

The outcome timing raises an interpretive question: measurements were intended at baseline and 2 hours after dosing. A result would need to clarify how those repeated measurements were summarized and compared across groups. The registry does not report that analysis specification, and its note indicates that the primary outcome’s multiple time points were not reduced to a single comparison. That makes a precise treatment-effect interpretation unavailable from the posted information.

Finally, the safety counts illustrate how small group denominators constrain what event counts can establish. Zero recorded serious events is a useful description, but it cannot by itself characterize the range of possible risks or support a precise comparison. These statistical distinctions help keep the interpretation aligned with what the record actually reports: the trial’s structure and recorded counts, rather than unreported outcome effects.

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 principal limitation for interpreting this trial from the registry record is that numerical primary outcome results are not reported. Group means, standard deviations, changes from baseline, contrasts, and uncertainty estimates are all absent. The record therefore does not allow readers to assess the direction, size, or precision of any difference in resting pupil diameter.

The registry describes participants with osteoarthritis of the knee or hip and healthy subjects for comparison, but does not report the numbers in each population or explain how those participants were distributed among treatment groups. Baseline characteristics and further eligibility details are not reported in the registry record. This limits understanding of the study population and the applicability of any potential findings.

The primary outcome is measured at baseline and 2 hours after dosing, and the record notes multiple categories or time points without reducing them to one comparison. It does not report the analysis model, exact contrast, missing-data approach, analysis population, or multiplicity handling. It also does not identify which roles were masked or describe the allocation procedure. These missing details limit assessment of the analysis and its reproducibility.

The record lists enrollment of 30, but does not report a sample-size justification for the original design. The separate planning statement is a calculation illustration based on the observed effect; numerical planning values are not reported. The safety record reports zero serious and other adverse events in each group, but does not give event definitions, monitoring duration, or event descriptions. These limitations constrain both the outcome and safety interpretations without establishing that any unreported method or event was absent.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Pain Expectations in Subjects With Osteoarthritis — NCT02155257.
• Registry record last updated 2019-03-07; status last verified 2019-02.
• Results first posted 2019-03-07.
• 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 NCT02155257, “Pain Expectations in Subjects With Osteoarthritis,” a completed Phase 4 randomized, triple-masked, parallel-group feasibility study sponsored by Wake Forest University Health Sciences. It lists enrollment of 30 and three one-time oral interventions: modafinil 200 mg, gabapentin 900 mg, and placebo. The study began in 2014-07 and reached primary completion in 2017-10.

The primary outcome is resting pupil diameter in millimeters, measured at baseline and 2 hours after dosing using an infrared camera. The stated research purpose concerns altering pain expectations and examining pupil size and thermal heat responses. Numerical primary outcome results and the details needed to interpret a treatment comparison are not reported in the registry record.

The safety record lists 10 participants at risk in each group, with zero serious adverse events, zero other adverse events, and zero deaths in each group. These counts describe the posted record and do not establish comparative safety. The statistical planning statement is an illustration, not a report of observed power or the original design justification.