The Effect of Chronic Pain on Delay Discounting in Methadone Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Effect of Chronic Pain on Delay Discounting in Methadone Patients (NCT04473950), a randomized phase 1 study. The primary outcome is Delay Discounting of Money Rate (k).

2. Clinical Question

The clinical and behavioral question is whether delay discounting differs in methadone-maintained patients with chronic pain compared with those without chronic pain, and whether it changes in relation to the naloxone and placebo sessions. Delay discounting describes the tendency to prefer a smaller reward sooner rather than a larger reward later. The registry summary frames this tendency as an aspect of impulsive decision making, which could be relevant to understanding behavior in people with opioid-use disorder.

The registry describes chronic pain as a factor that may be associated with treatment challenges and illicit substance relapse, but those statements are background rationale, not findings from this trial. The study is described as developmental research. Its stated questions include whether decision making is more impulsive during opioid withdrawal and whether catastrophizing modifies the relationship between withdrawal and impulsive decision making among patients with chronic pain and opioid-use disorder. The record does not report results that answer these questions.

3. Trial Design

NCT04473950 is a Phase 1, randomized, triple-masked, parallel-design study sponsored by the University of California, San Francisco. The registry lists an enrollment of 10 and a status of terminated. The recorded study start is 2020-01-08, and the primary completion date is 2022-10-06. The reason for termination is not reported in the registry record.

The registry lists naloxone hydrochloride and placebo as drug interventions. It also describes a Pain Group of methadone-maintained patients with chronic pain and a No Pain Group of methadone-maintained patients without chronic pain. Each pain-status group is associated with a placebo session and a naloxone session in the adverse-event record. The record does not explain how participants were allocated, how the parallel-design label relates to these session listings, or which people were masked to which intervention. Those details are not reported in the registry record.

The stated purpose is to study delay discounting and its relationship to chronic pain and opioid withdrawal. The registry describes a planned assessment of the k-value approximately 30 minutes after study medication administration during each session. Secondary outcomes include peak pain on a Visual Analog Scale, peak Clinical Opiate Withdrawal Scale rating, peak Subjective Opiate Withdrawal Scale rating, and peak increase from baseline pupil diameter.

Although the study has a randomized designation, the pain-status groups are described by whether participants have chronic pain, not as randomized pain interventions. The record does not provide enough detail to determine the allocation sequence, the visit schedule, the participants’ exact exposure sequence, or how the pain groups were constituted. A protocol, detailed statistical analysis plan, and explanation of the termination 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

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 Delay Discounting of Money Rate (k), measured over k will be calculated from the same series of discounting questions that will be asked once each session at approximately 30 minutes after study medication administration..

The primary endpoint is delay discounting of money rate, represented by the k-value. The registry describes delay discounting as the relative preference for a smaller, sooner reward over a larger, later reward. Choices across different delays are used to quantify how much a future reward is devalued over time. In the registry’s description, a larger k-value indicates greater devaluation of future rewards and is associated with more impulsive behavior. The measure has no units and is described as ranging from zero to infinity.

This outcome is used because it provides a behavioral measure of choices involving rewards at different times, rather than relying only on a broad description of impulsivity. In the study’s rationale, impulsive decision making is relevant to understanding behavior in people with opioid-use disorder and possible relationships with chronic pain and withdrawal. The registry specifies that k is calculated from the same series of discounting questions asked once each session, approximately 30 minutes after study medication administration.

The outcome definition explains what the measure is intended to capture, but it does not establish that a particular k-value was observed or that the value differed across groups or sessions. The registry record does not report primary-outcome estimates, variability, confidence intervals, or tests of group or session differences. The record also does not report the exact discounting questions or how responses were converted into k-values.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods are easiest to interpret when the outcome, comparison, analysis population, and uncertainty estimate are all clear. For this study, the primary outcome is a continuous measure: the delay-discounting rate k. The registry identifies the mean as the summary parameter and standard deviation as the dispersion measure. A mean describes the center of observed values, while a standard deviation describes how spread out individual values are around that mean. Neither is reported for the primary endpoint in the registry record.

What would a comparison estimate?

A comparison would need to specify which groups or conditions are being contrasted. Possible questions raised by the study description include differences between patients with and without chronic pain and differences associated with naloxone and placebo sessions. These are not interchangeable questions. A pain-group contrast concerns participants categorized by pain status, while a session contrast concerns the intervention conditions listed in the record. The registry does not report the primary-outcome contrasts or explain the analysis structure connecting these factors.

For a continuous endpoint, a model could estimate group means or a difference between means, depending on the study design and analysis plan. If observations are related within a participant, the analysis generally needs to account for that dependence; treating related observations as independent can produce misleading uncertainty. This is a general statistical consideration, not a claim about the analysis used in this study. The registry record does not report the model, the unit of analysis, or whether participant-level repeated observations were incorporated.

How should uncertainty be read?

A confidence interval gives a range of values that are reasonably compatible with the data and the assumptions of the method. Its width reflects precision: a wider interval indicates greater uncertainty about the estimated quantity. A point estimate alone cannot convey this uncertainty. For this trial, confidence intervals for the primary outcome are not reported in the registry record, and the endpoint analysis is not reported. It is therefore not possible to evaluate the precision of any primary-outcome contrast from the registry.

A significance test and a confidence interval answer related but different questions. A p-value summarizes how unusual the data would be under a specified null hypothesis and model. It does not tell readers the probability that the null hypothesis is true, nor does it convey the size or practical importance of an effect. The registry record reports no primary-outcome p-value. Without an estimate and uncertainty interval, a numerical significance result alone, even if available, would not provide a complete interpretation.

What do the design labels establish?

The registry identifies the study as randomized, triple-masked, and parallel. These labels describe intended design features, but do not reveal the allocation procedure, masking roles, or the operational details of the comparisons. The record describes pain-status groups and placebo and naloxone sessions, yet does not explain how these elements fit together with the parallel-design label. The design labels should therefore be reported as recorded, without inferring an unreported sequence, crossover structure, or allocation method.

Randomization can support balanced comparison of measured and unmeasured characteristics in expectation, but it does not guarantee balance in a small study. That is a general statistical principle. The registry lists enrollment of 10; it does not state the number contributing data to each endpoint or provide baseline characteristics with which to assess the groups. Nor does the record identify whether the pain-status groups themselves were randomized, and the descriptions characterize them by existing chronic-pain status rather than by an assigned intervention.

Why can over-dispersion matter?

Over-dispersion means that observed variability is greater than a statistical model expects. If a model underestimates variability, its uncertainty estimates can be too narrow, making apparent precision misleading. The relevance of over-dispersion depends on the data type and model. The primary endpoint is described as a continuous k-value summarized by a mean and standard deviation; the registry does not report a fitted model or a check for over-dispersion. Accordingly, over-dispersion cannot be diagnosed from the record. More generally, the form and range of k-values may affect modeling choices, but the record does not provide the observed values or distribution.

What do the planning assumptions mean?

The registry’s planning description refers to a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It describes effects as fractions of an observed effect and distinguishes participant counts per arm from total event counts for time-to-event planning. These are planning assumptions, not reported trial outcomes. Since no observed primary effect or calculated planning values are available in the registry record, a target sample size cannot be assessed from these details. Sample-size planning illustrations are not observed power, and post hoc power is not a substitute for an estimate with a confidence interval.

The registry record does not report a primary analysis method, a prespecified estimand, a covariate-adjustment strategy, or a sensitivity analysis. It also does not report the handling of missing observations. Without these details, it is not possible to judge how a reported estimate would relate to the intended scientific question or how robust it would be to analytic choices. The central methodological limitation is that the registry lists the outcome definition but no primary-outcome analysis.

10. Multiplicity, Missing Data and Analysis Populations

The study summary raises several related questions: the relationship between chronic pain and impulsive decision making, the relationship between withdrawal and decision making, and whether catastrophizing modifies the withdrawal association. The registry also lists a primary outcome and secondary measures of pain, opioid withdrawal, and pupil diameter. When several outcomes, comparisons, or time points are examined, multiplicity can increase the chance of at least one apparently notable finding by chance. Methods such as prespecifying a primary contrast, adjusting for multiple testing, or treating secondary analyses as exploratory can help make interpretation clearer. The registry does not report a multiplicity strategy, a hierarchy of hypotheses, or a detailed statistical analysis plan.

Missing-data methods are also not reported in the registry record. The record does not state how incomplete discounting questionnaires, missed sessions, or unavailable outcome measurements would be handled. In general, a complete-case analysis uses only participants with the required observed data, whereas other methods may use assumptions about the missingness process. Different approaches can lead to different estimates when missingness is related to participant characteristics or outcomes. No specific approach should be attributed to this study without a registry description or analysis documentation.

Analysis populations are not defined in the record. It is not reported whether the planned analysis would include all randomized participants, only participants who completed a session, or another group. The enrollment of 10 does not establish how many contributed to each outcome analysis. The registry lists zero analyses, so it provides no analyzed sample size for the primary endpoint. These omissions limit assessment of both the risk of selective analysis and the generalizability of any eventual estimate.

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.

Most frequent non-serious adverse event terms

The registry reports serious adverse events and other adverse events separately for each pain-status group and session. For the Pain Group, placebo session, 6 were at risk for serious events and 0 were affected; 6 were at risk for other events and 1 was affected. For the Pain Group, naloxone session, 6 were at risk for serious events and 0 were affected; 6 were at risk for other events and 2 were affected. No deaths are listed in either entry.

For the No Pain Group, placebo session, 4 were at risk for serious events and 0 were affected; 4 were at risk for other events and 1 was affected. For the No Pain Group, naloxone session, 4 were at risk for serious events and 0 were affected; 4 were at risk for other events and 0 were affected. No deaths are listed in either entry.

These are registry counts for the listed group-session entries. The record does not give event descriptions, timing, severity details for other events, or an explanation of whether the same participants contribute to more than one session entry. The entries therefore should not be added or treated as independent participant groups. The reported absence of serious events in these entries does not establish the absence of risk, particularly in a study with enrollment of 10. The safety record is descriptive and does not establish a causal comparison between naloxone and placebo.

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

The registry establishes that NCT04473950 was designed to investigate delay discounting in methadone-maintained patients with and without chronic pain, with naloxone and placebo listed as interventions. It defines k as a measure of devaluation of delayed rewards and describes larger values as associated with more impulsive behavior. It also records secondary measures related to pain, opioid withdrawal, and pupil diameter. These details explain the scientific motivation and the intended measurement.

The registry does not report primary-outcome estimates or analyses. It therefore does not establish whether chronic pain was associated with a higher or lower k-value, whether values differed between naloxone and placebo sessions, or whether withdrawal or catastrophizing related to decision making. It also does not show the size or precision of any such association. No conclusion about a difference, no difference, or the importance of a difference can be drawn from an endpoint analysis that is absent from the record.

The study’s terminated status and enrollment of 10 are relevant context, but the reason for termination and the number of participants with analyzable endpoint data are not reported in the registry record. Termination alone does not explain the missing analysis or indicate what the findings would have been. Likewise, the adverse-event counts do not substitute for the missing behavioral results.

In general, a small study may be useful for developing measurement procedures or generating hypotheses, but estimates from a small sample can be imprecise. That general point does not determine the precision of this study’s outcome, because its primary estimates and uncertainty measures are not reported. The record supports a description of the research question and design labels, not a conclusion about the outcome or the effects of either intervention.

13. Why This Trial Matters Statistically

This trial is statistically interesting because it brings together a behavioral outcome, pain-status groups, and intervention sessions in a population maintained on methadone. The primary endpoint, delay discounting of money, is a continuous measure intended to quantify preferences for immediate versus delayed rewards. Its interpretation depends not only on the value of k but also on how the values were obtained, how observations are grouped, and how uncertainty is estimated.

The registry’s design labels and group descriptions raise an important reporting issue. It identifies the study as randomized, triple-masked, and parallel, while also listing pain-status groups and placebo and naloxone sessions. Clear reporting of allocation, masking, session structure, and the intended contrasts is needed to understand what a treatment or group estimate would represent. Those implementation details are not reported in the registry record.

The record also illustrates why an endpoint definition is not equivalent to an endpoint result. A detailed description of what k measures helps readers understand the intended construct, but inference requires observed estimates, a specified analysis, and a description of uncertainty. With zero analyses listed and no primary-outcome estimates, the central statistical question remains unanswered in the registry.

Finally, the study’s modest enrollment makes transparent reporting of participant flow and missing observations particularly important. The registry does not report the number contributing data to each analysis or how missing outcomes were handled. Those details would be necessary to assess the precision and representativeness of any eventual findings. These are general considerations for interpreting a small behavioral study, rather than claims about analyses that were performed.

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.

Several trial-specific limitations follow from the registry record. The primary outcome is defined, but no endpoint results, group summaries, effect estimates, confidence intervals, or hypothesis tests are reported. The record lists zero analyses and notes that the primary outcome has several categories or time points rather than a single reduced comparison. This prevents a direct statistical assessment of the central research question.

The registry does not explain the relationship between its randomized, triple-masked, parallel-design labels and its descriptions of pain-status groups and placebo and naloxone sessions. It does not report the allocation procedure, masking roles, detailed session sequence, or the intended primary contrast. Consequently, the design and analysis cannot be reconstructed from the registry description alone.

Although enrollment is listed as 10, the record does not report participant flow, the number with complete k-values, or the analysis population. Missing-data handling and any sensitivity analyses are not reported in the registry record. The reason for termination is also not reported. These omissions leave uncertainty about how many observations could inform the outcome and why the study stopped.

The registry does not provide the prespecified statistical analysis plan, multiplicity approach, covariate adjustment, or sample-size justification. It describes general planning assumptions, but no observed effect or calculated sample-size illustrations are included in the available record. The adverse-event entries lack descriptions of the non-serious events and do not explain whether individuals recur across session entries. These limits constrain interpretation of both efficacy-related questions and safety summaries.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Effect of Chronic Pain on Delay Discounting in Methadone Patients — NCT04473950.
• Registry record last updated 2025-03-26; status last verified 2025-03.
• Results first posted 2025-03-26.
• 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

NCT04473950, “The Effect of Chronic Pain on Delay Discounting in Methadone Patients,” is listed as a Phase 1, randomized, triple-masked, parallel-design study sponsored by the University of California, San Francisco. It enrolled 10 and is marked terminated. The recorded start date is 2020-01-08, and primary completion is dated 2022-10-06.

The study concerns methadone-maintained patients with opioid-use disorder, with groups described as having or not having chronic pain. Naloxone hydrochloride and placebo are listed as interventions. The primary endpoint is delay discounting of money rate, measured by k approximately 30 minutes after study medication administration during each session. Secondary outcomes concern pain, opioid withdrawal, and pupil diameter.

The registry reports no primary-outcome analyses or endpoint estimates. The reason for termination, analysis population, missing-data approach, and detailed statistical plan are not reported in the registry record. Safety entries list no serious adverse events or deaths in the recorded group-session entries, alongside some other adverse events.