The Neurobiology of Expectancy and Pain Perception: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Neurobiology of Expectancy and Pain Perception (NCT01575106), a na na study. The primary outcome is Subjective Response to Pain (0-20 Visual Analogue Scale).

2. Clinical Question

3. Trial Design

The record describes a completed, single-group study sponsored by Massachusetts General Hospital. Its title concerns expectancy and pain perception, and its official title describes brain imaging in connection with the analgesic effect of lidocaine and the hyperalgesic effect of capsaicin. The brief summary says functional magnetic resonance imaging was intended to investigate how contextual learning and expectation relate to pain experience within the same cohort and study session.

The listed intervention is the application of heat pain using TSA or CHEPS. The record says participants received heat pain before and after applications of a neutral cream. Participants were told that one application was lidocaine, one was capsaicin, and one was neutral. The primary pain outcome was measured in session 3. Participants had up to three weeks to complete the three sessions. The listed primary-outcome timeframe is Weeks 1-3.

The study has one cohort, and the registry identifies the model as single group. Allocation is recorded as not applicable, and masking is listed as none. These design features matter when interpreting comparisons: the record does not establish randomized, blinded groups receiving different interventions. The cream labels form part of the expectancy context described in the study, not evidence of separate randomized arms.

The registry lists an enrollment of 38 and a completed status. It lists two outcome measures but provides no reported inferential analyses. It does not report a protocol-based sample-size justification, details of interim analyses, or a statistical analysis plan. The design and results in the registry therefore support description of the study question and outcome collection, but not an estimate of a treatment effect from the posted 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 Subjective Response to Pain (0-20 Visual Analogue Scale), measured over Weeks 1-3.

The primary endpoint is subjective response to pain, measured as pain intensity on a 0–20 Visual Analogue Scale. The scale is described as ranging from 0 for no pain to 20 for intolerable pain. Participants received heat pain before and after the cream applications and rated its intensity. The registry says the pain intensity for each cream was averaged among participants for both the pre-treatment and post-treatment ratings in session 3.

A subjective rating is relevant to a study focused on pain perception because it records participants’ reported experience rather than relying only on an instrument-based measure. It can capture the experience the study is designed to investigate, including the possible role of expectation described in the record. It is not, by itself, a direct measurement of brain activity. The brief summary mentions functional magnetic resonance imaging, but the primary endpoint described in detail is the pain rating.

The registry characterizes the endpoint as a mean of a continuous measure and identifies the dispersion statistic as the standard error. A mean describes the average rating; a standard error describes the precision of an estimated mean, rather than the spread of individual participants’ ratings. The endpoint description does not provide the mean ratings or standard errors. The registry also does not report an estimated contrast, confidence interval, or test for differences across pre-treatment and post-treatment ratings or cream labels. Thus, the endpoint is clearly described, but its observed values and uncertainty are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is continuous: pain intensity is recorded on a 0–20 Visual Analogue Scale and summarized using a mean. A mean represents the arithmetic average of the observations included in an analysis. It does not show the range of individual experiences, whether ratings cluster closely together, or whether a few high or low ratings influence the average. Those features require additional descriptive information, which is not reported in the registry record.

What does the standard error describe?

The registry identifies the standard error as the dispersion statistic for the primary outcome. In general, a standard error describes the sampling precision of an estimated quantity, such as a mean. It is not interchangeable with a standard deviation: a standard deviation describes variability among individual observations, whereas a standard error concerns uncertainty in an estimate. A standard error can help readers understand how precisely a mean has been estimated, but it does not by itself show the range of individual ratings.

Here, neither the means nor the standard errors are reported. Consequently, the precision of the average ratings cannot be assessed. The record also does not provide confidence intervals. In general, a confidence interval presents a range of values compatible with the data and the statistical procedure used, subject to its assumptions. It helps communicate uncertainty around an estimate, but it cannot be reconstructed from the registry information.

How should within-person measurements be considered?

The study description concerns the same cohort and refers to ratings before and after cream applications. Such repeated observations from the same person are generally related: a participant’s ratings under one condition may be more similar to their other ratings than to ratings from another participant. General statistical methods for repeated measurements account for this dependence. Treating related observations as though they came from unrelated people can misstate uncertainty.

The registry record does not specify the inferential model, whether the analysis used paired contrasts, or how within-person dependence was handled. It says that ratings for each cream were averaged among participants for pre-treatment and post-treatment observations in session 3, but it does not explain the statistical procedure used to compare those values. Because no analysis is reported, there is no basis to attribute a particular model or testing method to the study.

Why do the cream labels matter?

The study’s stated interest is contextual learning and expectation. Participants were told that the neutral cream applications represented lidocaine, capsaicin, or neutral cream. This is distinct from a conventional trial in which participants are randomly allocated to separate active-treatment and control groups. The record identifies one cohort and no allocation procedure. Comparisons associated with the labels would therefore need to be understood in the context of the study’s expectancy design, not as independent arm comparisons.

In general, an analysis of repeated conditions can be affected by order, carryover, learning, and changes over time. These are methodological considerations, not findings about this study. The registry record does not describe condition order, randomization of order, washout procedures, or methods for addressing such issues. It would be inappropriate to assume that any particular safeguard or adjustment was used.

What does the planning illustration mean?

The record describes a sample-size planning illustration based on the observed effect. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and detection of a stated fraction of the observed effect. These are planning assumptions, not a report of the study’s original design rationale. The described study is single group, so the assumed two-arm allocation does not match the study structure in the registry.

In general, a planning calculation estimates the sample size that might be needed for a future study under specified assumptions. When based on an effect estimated in the same data, it is an illustration rather than independent evidence of design adequacy. It is not observed power. The record does not report the actual-study sample-size justification, and no planning result should be treated as a substitute for the unreported outcome estimates and their uncertainty.

What analyses are available?

The registry lists no reported analyses. It does not identify a test statistic, model, adjustment covariates, confidence-interval method, or decision threshold for interpreting the primary outcome. Nor does it report a statistical plan specifying which contrasts were primary. General statistical principles can explain why those details matter, but they cannot supply missing study-specific methods.

Multiplicity is relevant whenever multiple outcomes, conditions, or contrasts are examined. Testing many questions can increase the chance that at least one result appears unusual by chance. In general, an analysis plan may define a primary contrast or use an adjustment approach to address this concern. The record lists two outcome measures but does not report a multiplicity strategy or analyses. No claim about adjustment can therefore be made.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists two outcome measures and no reported analyses. It does not identify a prespecified hierarchy among outcomes, a primary contrast beyond the named primary endpoint, or an adjustment for testing multiple outcomes or condition-specific comparisons. In general, examining multiple outcomes or contrasts creates a multiplicity concern: the more questions tested, the greater the opportunity for chance findings. A prespecified analysis plan or an appropriate adjustment can help readers understand how that issue was handled. No such method is reported.

The endpoint description says the pain ratings were averaged among participants for pre-treatment and post-treatment observations in session 3. It does not state how many participants contributed ratings to each average, whether all enrolled participants completed the endpoint, or how missing observations were handled. The enrollment figure does not establish the endpoint-specific analysis population. The record does not report whether missing values were excluded, imputed, or managed using another method.

The registry also does not describe how participants were selected for the analysis, whether any data were excluded, or whether analyses followed a prespecified intention-to-treat or other population definition. Those terms should not be inferred from the single-group design. Without an analysis population and missing-data description, readers cannot assess whether the reported averages, if available, would represent all enrolled participants or a subset with observed ratings.

These omissions limit interpretation independently of whether a numerical result appears elsewhere. Results require context about the endpoint, analysis population, missingness, and multiplicity. Since the registry does not report analyses or these methodological details, it is not possible to judge whether the primary question was tested as planned or how robust any result would be to alternative analysis choices.

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 adverse-event information lists separate entries titled Heat Pain and Cream. For Heat Pain, the record reports zero serious events among 38 at risk, one other event among 38 at risk, and zero deaths. For Cream, it reports zero serious events among 38 at risk, zero other events among 38 at risk, and zero deaths. The registry does not list any serious-event terms.

These figures are counts recorded in the registry, not estimates of comparative risk. The study is single group, and the entries do not establish randomized, independent comparison groups. They should not be interpreted as a controlled safety comparison between heat pain and cream. The record does not provide event descriptions, timing, relatedness assessments, or details about how events were collected. It also does not report whether the other event was considered related to the study procedures.

Zero reported serious events does not establish that no serious event could occur; it describes what is recorded for this study. Likewise, the one other event in the Heat Pain entry cannot be attributed to heat pain from the registry figures alone. The event counts should be read as a limited description of what the record reports, not as evidence for a broader safety conclusion.

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

The record documents a study designed to examine pain perception in a context involving heat pain and expectations associated with cream labels. It identifies a subjective pain-rating endpoint, the scale used, and the session in which the endpoint was measured. These details clarify what the study set out to observe.

The record does not provide the primary endpoint values, estimates of differences, measures of uncertainty, or reported inferential analyses. It therefore does not show whether pain ratings changed before and after the cream applications, whether ratings differed across the labels, or how large or precise any difference might have been. The study’s stated scientific aim should not be mistaken for a reported result.

The single-group design and lack of masking are important context. The record describes participants receiving neutral cream while being told it represented different substances. It does not describe randomized treatment arms. Consequently, the results, if reported elsewhere, would need interpretation in light of the expectancy context and the study’s actual comparison structure. The registry information does not support a conventional claim that one randomized treatment group outperformed a control group.

The record also does not report participant-level variability, endpoint completion, missing-data methods, or a statistical analysis plan. Without those details, readers cannot assess whether an average reflects the full enrolled cohort, how much individual ratings varied, or whether statistical uncertainty was handled appropriately. The sample-size planning assumptions do not fill those gaps and are not observed power.

The most defensible interpretation is limited: the registry describes an investigation of expectancy and pain ratings, but its posted results do not quantify the primary outcome. No conclusion about the magnitude, direction, precision, or causal interpretation of a change in pain rating follows from this record alone.

13. Why This Trial Matters Statistically

This study is statistically interesting because its stated question concerns the relationship between expectation and subjective pain perception. Such a question highlights the importance of distinguishing an observed rating from the context in which the rating was collected. The record describes participants receiving neutral cream under different labels, making the framing of the conditions central to understanding the study question.

The design also illustrates why a single-group repeated-measures study should not be read as a parallel-group trial. Participants in the same cohort can contribute ratings under more than one condition, and those observations may be statistically related. Appropriate interpretation depends on how repeated measurements and within-person dependence are handled. The registry does not report the analysis method, so that aspect cannot be evaluated from the record.

Measurement and reporting are equally important. The Visual Analogue Scale gives a defined measure of subjective pain intensity, while the mean and standard error would describe an average and its precision. Yet the registry does not report the values needed to assess either. This makes clear that naming an endpoint is not enough to convey evidence: readers also need estimates, uncertainty, and a transparent account of the analysis population and methods.

The planning illustration provides another useful lesson. Its assumptions describe a two-arm calculation, whereas the registered study is single group. Planning illustrations can inform future research under explicit assumptions, but they do not explain the original study’s sample-size rationale or establish observed power. The contrast between the stated planning setup and the actual design underscores the need to keep hypothetical calculations separate from trial findings.

Finally, the adverse-event entries show why raw counts need design context. Counts in separate registry categories do not automatically establish comparative risks, especially when the record does not describe randomized groups. Statistical interpretation depends not only on numbers, but on how the data arose and what analyses were conducted.

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 of interpreting this trial from the registry record is that the primary outcome results are not reported. The record gives the scale and measurement description but not the mean ratings, standard errors, contrasts, confidence intervals, or p-values. Therefore, the size, direction, and precision of any effect cannot be assessed.

The study is listed as single group, with allocation not applicable and masking none. The cream conditions are described as neutral cream applications presented with different labels, rather than separately randomized arms. This limits interpretation as a treatment comparison and makes it especially important to know the condition order and analysis approach. The registry does not report those details.

The outcome was measured in session 3, while participants could complete three sessions within up to three weeks. The record does not specify how session completion, timing variation, or incomplete observations were handled. It also does not state the number contributing to each endpoint average or define the analysis population.

Although the brief summary refers to functional magnetic resonance imaging, the available detailed endpoint description concerns subjective pain intensity. The second listed outcome measure is not described in the information available for this analysis, and the registry lists no reported analyses. Thus, the imaging component and its relationship to the reported outcomes cannot be evaluated from the record.

Finally, no statistical analysis plan, multiplicity approach, missing-data method, or sample-size justification for the actual design is reported. The planning assumptions refer to a two-arm calculation and should not be mistaken for the study’s design rationale. These gaps prevent a complete assessment of the study’s statistical methods and results.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: The Neurobiology of Expectancy and Pain Perception — NCT01575106.
• Registry record last updated 2017-10-13; status last verified 2017-01.
• Results first posted 2017-10-13.
• 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, single-group study sponsored by Massachusetts General Hospital, with an enrollment of 38. Its stated focus is how contextual learning and expectation relate to pain experience. The listed intervention is heat pain applied using TSA or CHEPS; the outcome description concerns ratings before and after neutral cream applications presented as lidocaine, capsaicin, or neutral cream.

The primary endpoint is mean subjective pain intensity on a 0–20 Visual Analogue Scale, measured in session 3. The record identifies the standard error as the dispersion statistic and gives Weeks 1-3 as the timeframe. It does not report the endpoint values, inferential analyses, or detailed methods for missing data and multiplicity.

The adverse-event entries report zero serious events and zero deaths in both listed categories, with one other event recorded under Heat Pain and none under Cream. These entries do not establish a controlled safety comparison. Overall, the registry describes the study question and measurement, but does not report enough outcome or analysis information to quantify the primary result.