Effectiveness and Feasibility of Patient Controlled Analgesia in the ED: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness and Feasibility of Patient Controlled Analgesia in the ED (NCT01775371), a randomized na study. The primary outcome is Rate of Change in Pain Intensity Per Hour.

2. Clinical Question

3. Trial Design

The study is registered as a randomized, open-label, parallel-group trial of PCA versus usual opioid care for pain in the emergency department. Its status is completed. The registry lists enrollment as 636 and records the start as 2013-04 and primary completion as 2016-02. Phase is listed as NA. Albert Einstein College of Medicine is named as the sponsor.

Random allocation supports a comparison between treatment groups by reducing the likelihood that baseline differences are systematically assigned to one group. In general, this benefit depends on how randomization was generated and implemented; those details are not reported in the registry record. The parallel-group model means participants were assigned to a treatment group for the comparison rather than crossing between the listed interventions. The record does not describe the allocation ratio or any stratification factors.

Masking is listed as none. Participants and clinical staff therefore were not masked according to the registry entry. For a pain-rating outcome, awareness of treatment assignment could influence expectations, reporting, or care decisions. That possibility is a limitation to consider, not evidence that the recorded pain scores were biased in a particular direction.

The PCA arm is described as receiving a morphine loading dose of 0.1 mg/kg and access to a 1 mg demand dose every 6 minutes. Usual care is described as provider-determined opioid analgesia. The record does not provide a more detailed account of usual-care dosing or of how consistently either intervention was delivered.

The study’s stated objective included comparing effectiveness and safety and describing feasibility, including patient and provider acceptance. The primary outcome was the rate of change in pain intensity per hour over the specified period. Secondary outcomes listed in the record include participants with one or more adverse events and patient satisfaction with pain management. Detailed eligibility criteria, site-level information, recruitment procedures, and the randomization implementation are not reported in the registry record.

4. Participant Flow and Accounting

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

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients enrolled

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 Rate of Change in Pain Intensity Per Hour, measured over 1.5 hours.

The primary endpoint is the rate of change in Numerical Rating Scale pain intensity per hour, measured between 30 minutes and 120 minutes after baseline. The scale runs from 0, meaning no pain, to 10, meaning worst possible pain. The registry defines the change as the score at 30 minutes minus the score at 120 minutes. Under that definition, a positive value reflects a lower pain score at the later assessment than at the earlier assessment.

A change-over-time endpoint focuses on the trajectory of pain during the specified observation period, rather than only the score at a single assessment. Dividing a change by elapsed time expresses that trajectory as a rate, which can make the result interpretable as change per hour. In general, repeated pain assessments can help describe whether pain is declining and how quickly, while a single score cannot describe the pattern across assessments.

The endpoint is relevant to the study’s stated question because PCA permits patient requests for additional analgesia, while usual care is determined by the provider. A rate of change can capture differences in the timing of pain reduction during the monitored interval. However, this endpoint is limited to the stated period and scale. It does not alone describe pain beyond 120 minutes, patient satisfaction, feasibility, or all aspects of safety. The registry identifies the primary population as all patients enrolled; whether all enrolled participants contributed measurements at both assessment times is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint represent?

The outcome is continuous: it is the mean rate of change in pain intensity, rather than a count of participants reaching a threshold. The registry defines the rate using Numerical Rating Scale scores at 30 minutes and 120 minutes after baseline. The score at the earlier assessment minus the score at the later assessment gives the stated change. A positive rate therefore represents a fall in the pain score during the interval. Reporting the measure per hour describes the pace of change over time, but it remains an average summary of the group’s scores.

In general, a continuous endpoint retains information across the scale instead of reducing observations to categories such as improved or not improved. Its interpretation depends on the scale, the timing of assessment, and the construction of the change measure. The meaning of a group mean does not imply that individual responses are uniform.

How should the confidence intervals be read?

The registry reports a 95% confidence interval for each group mean and for the between-group mean difference. For PCA, the mean rate was 1.3, with a 95% confidence interval from 1.0 to 1.6; for usual care, it was 0.3, with a 95% confidence interval from 0.0 to 0.6. The reported mean difference was 1.0, with a 95% confidence interval from 0.6 to 1.5.

In general, a confidence interval conveys statistical uncertainty in an estimated quantity under the analysis method’s assumptions. It is not a range containing a specified share of individual outcomes. A narrower interval indicates greater precision than a wider interval on the same scale, while the interval’s location indicates which values are compatible with the estimate and method. The between-group interval is the relevant interval for the contrast; the group-specific intervals are estimates of the means within each arm.

What does the p-value add?

The reported test is a two-sided Z-test, with p < 0.001. In general, a p-value describes how unusual data at least as inconsistent with a null comparison would be if that null model and the test assumptions were correct. It does not measure the probability that the observed result is due to chance, and it does not measure the magnitude or practical importance of a result. The estimated mean difference and its confidence interval provide information about magnitude and precision that the p-value alone does not.

The registry does not describe the underlying standard-error calculation, distributional checks, or any adjustment to the test. Those details are not reported in the registry record, so the posted test can be described but not independently audited from the record’s summary statistics alone.

What does randomization contribute?

Randomized allocation is intended to make treatment groups comparable, on average, with respect to factors present before assignment. In general, randomization supports causal interpretation when allocation is implemented as planned, follow-up is appropriate, and analysis preserves the comparison created by assignment. The registry identifies the trial as randomized but does not report the sequence-generation method, concealment procedures, or whether all participants were analyzed in their assigned groups. The absence of masking is reported, which is relevant for a subjective outcome such as a pain rating.

The study used a parallel model and compared PCA with provider-determined usual opioid care. This is a pragmatic contrast between the assigned approach and the care process described for the comparator, not a comparison of identical dose schedules. Details of treatment adherence, additional co-interventions, and protocol deviations are not reported in the registry record.

What can sample-size illustrations tell readers?

In general, a sample-size calculation is a planning exercise under assumptions about the effect to detect, variability, significance level, allocation, and statistical method. It is not a measure of the probability that a completed trial detected an effect. The registry’s planning illustration is described as using a two-sided significance level of 0.05, equal allocation, and a normal approximation, with effects expressed as fractions of the observed effect. The illustrations are planning scenarios, not observed power and not the trial’s own design justification. The registry does not report a sample-size justification for the original trial in this record.

Because the planning scenarios use the observed effect as their reference, they should not be read as independent evidence that the effect is reproducible. Smaller assumed effects generally require more information to detect under otherwise comparable planning assumptions; this is a general statistical principle, not a result specific to the trial. The scenario values and other details not stated in the registry record are not inferred.

What is not specified about the analysis?

The registry lists five outcome measures and five analyses, and identifies the primary population as all patients enrolled. It does not report the full statistical analysis plan, the treatment of missing outcome measurements, covariate adjustment, sensitivity analyses, interim analyses, or the approach to multiplicity. These omissions limit assessment of how the reported result relates to all analyses that may have been planned or conducted.

In general, multiple outcomes or repeated statistical tests can increase the chance of at least one apparently notable result if no multiplicity strategy is used. That general concern does not establish that the reported result is false or that an adjustment was required; whether and how multiplicity was handled is not reported in the registry record. Similarly, missing data can affect an estimate if the availability of measurements is related to treatment or outcome, but the direction and size of any such effect cannot be inferred without details about missingness and the analysis.

10. Analyses Reported by the Sponsor

The sponsor-reported comparison is a mean difference in final values of 1.0, with a 95% confidence interval from 0.6 to 1.5 and p < 0.001, using a two-sided Z-test. This is consistent with the posted group means: the rate was 1.3 in the PCA arm and 0.3 in the usual-care arm. The unadjusted recalculation from the posted summary statistics does not identify a discrepancy with the sponsor’s reported comparison. The sponsor’s analysis is the primary reported inferential result.

The group means have their own 95% confidence intervals: 1.0 to 1.6 for PCA and 0.0 to 0.6 for usual care. These intervals describe uncertainty around each group mean; the interval from 0.6 to 1.5 describes the reported between-group mean difference. The reported p-value belongs to the comparison, not to either arm mean in isolation.

The registry does not give enough detail to reconstruct every element of the sponsor’s analysis, such as the variance estimation or handling of missing scores. The recalculation is unadjusted and based on the posted summary statistics, so it is not a substitute for a full analysis using participant-level data. Since the registry record does not flag a discrepancy, no conflicting recalculated result needs to replace the sponsor’s reported test. Interpretation remains subject to the limitations of the endpoint, the open-label design, and unreported analysis details.

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies the rate of change in pain intensity per hour as the primary outcome and lists five outcome measures and five analyses. It also lists patient satisfaction with pain management and participants with one or more adverse events as secondary outcomes. The record does not report whether the analyses were prespecified in a statistical analysis plan, how many comparisons were planned for each outcome, or whether any multiplicity adjustment was used.

In general, testing multiple outcomes or making multiple comparisons can increase the chance that at least one result appears statistically notable under a set of null effects. Methods for addressing this include defining a primary comparison in advance, adjusting significance thresholds, or treating secondary results as exploratory. These are general approaches; the registry does not say which, if any, was used for this trial. The primary comparison can be described on its own, but the available record does not establish how it fits into the full family of analyses.

The primary population is specified as all patients enrolled. That wording does not explain the actual analysis set or confirm that each enrolled participant contributed an evaluable score. The record does not report the amount or pattern of missing pain data, reasons for missing assessments, imputation methods, or sensitivity analyses. Because the endpoint is a change between assessments, interpretation depends on how observations at the relevant times were available and handled.

In general, missing-data methods rely on assumptions about why observations are absent. If missingness is related to pain, treatment assignment, or other participant characteristics, analyzing only observed measurements can differ from the result that would have been obtained with complete follow-up. No direction or magnitude of such an effect can be determined from the registry summary.

The record also does not report whether the analysis followed randomized assignment, whether any participants were excluded after randomization, or whether adjustments for baseline variables were used. These features should not be assumed. The combination of unreported multiplicity procedures and missing-data handling calls for restrained interpretation of the primary p-value and confidence interval, without negating the reported comparison.

12. 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.

Most frequent non-serious adverse event terms

The registry reports no serious adverse events in either group. It reports 7 other adverse events in the PCA group and 1 in the usual-care group. The at-risk counts listed for the safety summaries are 306 for PCA and 330 for usual care. Deaths are recorded as 0 in both groups.

These are event counts as classified in the registry, not a complete description of event types, timing, severity, or relatedness. The record lists no top serious adverse-event terms. It does not give further detail about the other adverse events in this summary, including their nature or whether participants experienced more than one event. Therefore the counts should not be expanded into claims about particular symptoms or causes.

In general, observing no serious events in a trial does not establish that the risk is absent. Safety estimates depend on the number of people observed, follow-up duration, event definitions, ascertainment, and the rarity of the events of interest. The registry does not report enough detail to characterize those elements fully. The absence of recorded serious events is a descriptive finding for this trial record, not proof of equivalent safety between the groups or a guarantee about other settings.

The study’s stated hypothesis anticipated similar safety, but the available serious-event counts alone do not establish similarity. A formal safety comparison, its uncertainty, and the handling of multiple safety outcomes are not reported in the registry record. The adverse-event counts should therefore be read alongside, rather than as a replacement for, the primary effectiveness result.

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

The posted primary result describes a greater mean rate of pain-score decline in the PCA group than in the usual-care group during the interval from 30 minutes to 120 minutes after baseline. The reported mean difference is 1.0 score per hour, with a 95% confidence interval from 0.6 to 1.5 and p < 0.001. The direction follows the registry’s definition of change: the score at 30 minutes minus the score at 120 minutes. These statistics describe the observed group comparison in the registered outcome.

The result does not mean that every participant receiving PCA had a faster decline, or that every participant receiving usual care had little or no decline. Group means do not display the full range of individual responses. Nor does the outcome mean that participants reached a particular pain level; it measures average change over the specified interval, not a threshold or an endpoint score alone.

The result also does not answer all of the trial’s stated questions. It does not by itself establish patient or provider acceptance, the feasibility of delivering PCA, patient satisfaction, or safety equivalence. The registry lists satisfaction and adverse events as secondary outcomes, but the information available for interpretation is limited. No serious adverse events were recorded in either group, while other adverse events were recorded in both; these descriptive counts do not prove absence of risk.

Statistical evidence and clinical importance are related but distinct. In general, statistical significance describes compatibility with a null comparison under specified assumptions, while clinical importance concerns the relevance of the size and consequences of a difference. The registry record does not provide a threshold for a clinically important change or enough contextual detail to determine that question. The pain scale’s stated endpoints help explain the direction of the result, but do not establish how patients would value the observed difference.

Finally, interpretation is limited by the open-label design and by unreported details about missing observations, analysis populations, and multiplicity. The trial’s randomized design is relevant to the comparison, but the registry summary alone cannot resolve those issues or establish generalizability beyond the enrolled population and participating clinical settings.

14. Why This Trial Matters Statistically

This trial addresses a statistical challenge in emergency-department pain research: pain changes over time, while analgesic delivery may depend on patient requests or provider decisions. A rate-of-change endpoint makes the timing of the assessment part of the estimand. It asks about the pace of change during a defined interval, not simply the pain score at a single time. That distinction matters when comparing approaches that may differ in how and when analgesia is delivered.

The outcome is based on a numerical rating scale, and the registry explicitly defines both the scale’s direction and the subtraction used to form the change. Clear endpoint construction is essential because reversing the subtraction would reverse the interpretation of a positive result. Here, the stated definition allows the reported positive means and contrast to be read as a decline in pain score.

The randomized parallel-group design provides a structure for comparing treatment strategies, and the reported confidence interval conveys uncertainty around the difference in average rates. Presenting both an estimate and its interval is more informative than relying on a p-value alone. The open-label design is also an important statistical feature because patient-reported pain outcomes may be sensitive to expectations and knowledge of treatment assignment.

The record illustrates why effectiveness and safety require distinct evidence. The primary outcome estimates a difference in pain-score trajectory, while adverse-event counts describe recorded safety events. Neither measure substitutes for the other. Likewise, a completed trial with a statistically notable primary comparison does not resolve feasibility, satisfaction, missing-data, or multiplicity questions that are not fully described in the record.

For biostatisticians and clinical researchers, the case highlights the value of transparent reporting of endpoint definitions, analysis populations, missingness, and planned comparisons. Such detail is needed to evaluate precision, potential bias, and the scope of conclusions. The record supplies a clear primary endpoint definition and sponsor comparison, but leaves several analysis and implementation details unreported.

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 record identifies the trial as open-label, with no masking. Because the primary outcome is a patient-reported pain rating, awareness of treatment assignment could influence reporting or expectations. This is a potential source of bias, but the registry summary does not establish whether such an influence occurred or its direction.

The comparator is described as usual opioid analgesia determined by the provider, whereas the PCA arm has a specified loading dose and demand-dose arrangement. This captures a comparison of care strategies, but the registry does not describe the details or consistency of usual-care treatment. It also does not report treatment adherence, crossovers, additional analgesia, or protocol deviations, limiting assessment of how the assigned approaches were delivered in practice.

The endpoint is restricted to pain-score change between 30 minutes and 120 minutes after baseline. It does not summarize pain beyond that interval, and the record does not report whether every participant had measurements at both time points. Although the primary population is named as all patients enrolled, missing-data handling and the exact analysis population are not reported in the registry record.

The record lists a randomized design but does not report the sequence-generation or allocation-concealment methods. It also does not describe baseline characteristics, the statistical analysis plan, covariate adjustment, sensitivity analyses, or interim analyses. These details cannot be inferred. Multiplicity procedures for the listed outcomes and analyses are also not reported.

Enrollment is listed as 636, and the reported outcome groups have counts of 306 for PCA and 330 for usual care. The registry summary does not explain the relationship between enrollment and the endpoint-analysis population or whether all enrolled participants contributed data. The duration of follow-up for safety outcomes and detailed adverse-event descriptions are not given in the available record. Finally, the record does not provide enough site or eligibility detail to assess how broadly the findings apply beyond the study population and clinical centers.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effectiveness and Feasibility of Patient Controlled Analgesia in the ED — NCT01775371.
• Registry record last updated 2020-12-04; status last verified 2020-11.
• Results first posted 2020-12-04.
• 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

NCT01775371 is a completed randomized, open-label, parallel-group study sponsored by Albert Einstein College of Medicine. It compared patient controlled analgesia with provider-determined usual opioid analgesia among emergency-department patients with pain. The registry lists enrollment as 636, a start of 2013-04, and primary completion of 2016-02.

The primary outcome was the rate of change in pain intensity per hour, based on Numerical Rating Scale scores from 30 minutes to 120 minutes after baseline. The reported mean was 1.3 for PCA and 0.3 for usual care. The sponsor-reported mean difference was 1.0, with a 95% confidence interval from 0.6 to 1.5 and p < 0.001.

No serious adverse events or deaths were recorded in either group. Other adverse events were recorded as 7 with PCA and 1 with usual care. The registry identifies patient satisfaction and adverse events among the secondary outcomes. Details of missing-data handling, multiplicity, and several elements of the statistical analysis are not reported in the registry record.