Investigation of AVACEN Thermal Exchange System for Fibromyalgia Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Investigation of AVACEN Thermal Exchange System for Fibromyalgia Pain (NCT01619579), a na phase 2 study. The primary outcome is Widespread Pain Index (WPI) Score After 4 Weeks Treatment.

2. Clinical Question

The study asked whether daily use of the AVACEN Thermal Exchange System for 4 weeks would be accompanied by changes in fibromyalgia pain and functioning markers. The registry describes a hypothesis involving biomarkers and clinical and psychological assessment, but the listed primary endpoint is the Widespread Pain Index score after treatment. The record does not report that score or its change from baseline.

This is therefore a question about observed outcomes following treatment in an open-label, single-group study, not a randomized comparison of the device against a control. The registry's stated hypothesis proposed that changes in body temperature might affect sympathetic nervous system activity and thereby reduce fibromyalgia pain. That is the rationale recorded for the study, not a finding established by the reported endpoint. With no posted primary score, baseline value, or change estimate, the registry record does not allow readers to assess whether WPI scores changed, how large any change was, or how precisely it was estimated.

3. Trial Design

This Phase 2 study is titled “Investigation of AVACEN Thermal Exchange System for Fibromyalgia Pain” and is described in its official title as an open-label study of 4 weeks of treatment. The registry lists fibromyalgia as the condition and the AVACEN Thermal Exchange System as the intervention. It records a single-group model, allocation as NA, and masking as none. The trial status is completed, with a recorded start date of 2011-06 and primary completion date of 2012-05.

The treatment description states that participants with fibromyalgia used the device twice daily for 4 weeks. The registry's summary describes the device as non-invasive and says the user places a hand in a vacuum chamber and rests it on a heating element. It also presents a proposed pathway involving core body temperature and sympathetic nervous system activity. These statements describe the device and study rationale; the registry record does not provide a measured temperature result or evidence that this proposed pathway occurred.

The enrollment figure is 22. The primary outcome's population description notes that three participants withdrew for personal reasons and that their post-therapy data were not obtained. The record does not describe a control intervention for the primary endpoint. Although safety information is displayed under Treatment Group A and Treatment Group B, the overall study is identified as single-group, and the record does not explain those safety labels as separate efficacy arms. They should not be treated as randomized or otherwise comparable groups.

The registry lists three outcome measures but records zero analyses. The primary outcome is WPI score after 4 weeks. Results for that measure are not reported in the registry record. Details of the other outcome measures, analysis procedures, and analysis populations are also not reported. The registry record does not report a protocol-level explanation for the allocation entry, a sample-size justification, or an interim analysis plan.

4. Participant Flow and Accounting

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

Before assignment: Participants enrolled were diagnosed with FMS according to the 2010 ACR diagnostic criteria and were advised to refrain from stopping, changing, or starting any new treatment programs other than the study intervention. Patients who recently started, stopped, or changed pain or mood treatment were ineligible to enroll until three months had elapsed.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Enrolled population was diagnosed with FMS according to the 2010 ACR diagnostic criteria. Three participants withdrew from the study for personal reasons and their post-therapy data were not obtained.

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 Widespread Pain Index (WPI) Score After 4 Weeks Treatment, measured over 4 Weeks.

The primary endpoint is the Widespread Pain Index (WPI) score after 4 weeks of treatment, expressed in units on a scale. The registry describes the range as 0 to 19 points, with 0 identified as the lowest pain score and best outcome, and 19 as the highest pain score and worst outcome. Its description defines widespread pain as pain occurring in at least 2 contralateral body quadrants, in addition to the axial skeleton, for at least 3 consecutive months.

As a general explanation, an index such as the WPI provides a structured way to record the distribution of pain using a consistent scoring approach. The score is intended to represent the extent of widespread pain according to the registry's definition; it should not be confused with an independently reported measure of every aspect of pain, functioning, or quality of life. The registry's study summary mentions biomarkers and clinical and psychological assessment, but the WPI is the one outcome identified as primary in the record.

The endpoint title specifies a score after treatment, but no observed mean, full range, baseline score, or change estimate is reported. Consequently, the registry record does not show the participants' WPI results or how variable those results were. Without those values, the direction, magnitude, and precision of the primary endpoint cannot be evaluated from the record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design establish?

In a single-group study, outcomes are measured in a group receiving the intervention, without a concurrent control group described for the comparison. As a general statistical point, such a design can describe outcomes among participants who contribute measurements. It does not create the direct treatment-versus-control contrast that random assignment is intended to support. Changes over time may have more than one explanation, and a single-group result cannot by itself distinguish those explanations.

For this study, the registry identifies a single-group model, allocation as NA, and no masking. The primary outcome is a post-treatment WPI score. Because the registry does not report the score, there is no posted numerical outcome to describe. Even if an outcome value were posted, the open-label, single-group design would need to be kept in view when interpreting it. The record does not describe a comparator for the primary endpoint, so the results should not be framed as a randomized comparison.

What does the WPI measure?

The WPI is described as a score from 0 to 19 points. The registry defines the relevant widespread pain pattern as pain in at least 2 contralateral body quadrants, in addition to the axial skeleton, for at least 3 consecutive months. It labels 0 the lowest pain score and best outcome, and 19 the highest pain score and worst outcome. In general, a scored measure gives researchers a standardized way to represent a feature of participants' health. Its usefulness depends on how it is measured and reported, and a single score should not automatically be interpreted as capturing all aspects of a condition.

The registry identifies the post-treatment WPI as the primary endpoint, but does not post a baseline score or the post-treatment result. It also does not report an estimate of change. Therefore, the endpoint description explains what was intended to be measured, but not what was observed.

Why does variability matter?

The primary outcome is specified as a mean with full range as its dispersion description. In general, a mean describes the arithmetic center of measured values, while the full range gives the lowest and highest observed values. A range can indicate how widely observations extend, but it does not show how values are distributed between those endpoints. A mean alone also does not show the full pattern of individual responses. The registry record does not report the mean or range, so neither the center nor the spread of the observed WPI scores can be examined.

General statistical interpretation also considers uncertainty around an estimate. A confidence interval is a range of values compatible with the data and a specified statistical procedure; it communicates precision as well as the estimated effect. The registry does not report a confidence interval for the primary endpoint. No such interval can be inferred from the endpoint description or enrollment figure alone.

What is over-dispersion, and is it relevant?

As a general concept, over-dispersion occurs when the variability in data exceeds what a statistical model assumes. It can make model-based uncertainty estimates too small if the model does not account for the extra variability. The registry record does not identify a count-based primary endpoint or report a model for the WPI outcome, so it does not provide a basis to say that over-dispersion was present or that a particular correction was used. This concept is relevant only as a general reminder that statistical methods should match the data and their variability.

What can planning calculations say?

General sample-size calculations estimate how many participants might be needed under specified assumptions about an effect, allocation, significance level, and statistical model. They are planning illustrations, not results from participants. The registry's planning description states that its illustrations use the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the detectable effect set as a stated fraction of the observed effect. It also distinguishes participants per arm for ordinary outcomes from total events for time-to-event outcomes. The registry record does not report the resulting planning values in the registry record for this analysis, nor does it establish that these assumptions formed the trial's original design. These illustrations must not be described as observed power or as a justification for the enrollment.

Why is the analysis plan important?

Statistical methods describe how researchers turn collected observations into estimates, quantify uncertainty, and address missing measurements. A prespecified analysis plan can also clarify which outcome is primary and how other outcomes are treated. The registry identifies three outcome measures and records zero analyses, but does not report the analysis methods for the primary endpoint. It does not state whether the endpoint was analyzed as an available-case mean, whether baseline values were used, or how missing observations were handled. These methods are not reported in the registry record, so they should not be assumed.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and identifies WPI score after 4 weeks as the primary endpoint. The other outcome measures and their results are not reported in the registry record. The record also lists zero analyses, so it does not provide analysis results or describe how the outcome measures were handled statistically.

Multiplicity refers, in general, to the interpretive issue that arises when several outcomes or statistical tests are examined. When many tests are considered, the chance of at least one apparently notable result can increase, depending on the testing plan. Researchers may address this with prespecified priorities or statistical adjustments, but the registry record does not report a multiplicity strategy. The primary designation helps identify the intended main endpoint; it does not reveal what tests were performed or whether any adjustment was used.

The population description states that three participants withdrew for personal reasons and that their post-therapy data were not obtained. Their primary endpoint values are therefore missing. The record does not report an analysis population, a missing-data method, or whether any sensitivity analysis was performed. As a general statistical point, missing outcomes can affect interpretation when the participants without measurements differ in relevant ways from those with measurements. The reason given for withdrawal is recorded, but the record does not provide information to determine whether missingness could have influenced the estimated result.

The registry record does not say whether all enrolled participants were included in any analysis or how adherence and other post-enrollment events were treated. Since no primary result or analysis method is posted, the effect of the missing measurements cannot be quantified. No assumption about the missing scores should be substituted for the absent data.

11. Safety Results

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

Other (non-serious) adverse events

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

The registry lists safety information under Treatment Group A and Treatment Group B. For Treatment Group A, the recorded risk count is 5 for serious events and 5 for other events, with zero serious events and zero other events reported. For Treatment Group B, the recorded risk count is 17 for serious events and 17 for other events, also with zero serious events and zero other events reported. Death counts are not reported in the registry record.

These are descriptive entries in the registry. A count of zero means that no event of that type is recorded for the stated risk group; it does not establish that the event is impossible or that a device is free of risk. General statistical interpretation recognizes that event counts from a limited study can be imprecise, particularly when few participants are represented. The record does not provide further information about event surveillance, duration of safety follow-up, or how these group labels relate to the single-group study design.

The two safety labels should not be treated as control and treatment arms or as a like-for-like comparison. The study is identified as single-group, and the registry marks the allocation as NA. The differing risk counts do not establish a comparative safety effect. The reported zero counts are best read as the adverse-event counts recorded for those labels, with the limitations of the registry description in mind.

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

The registry record establishes that a completed Phase 2, open-label study examined the AVACEN Thermal Exchange System in people with fibromyalgia. It describes twice-daily device use for 4 weeks and identifies WPI score after treatment as the primary endpoint. It also states that three participants withdrew for personal reasons and lacked post-therapy data. These are design and conduct details, not evidence about the size of a treatment effect.

The record does not report the primary WPI score, its baseline value, its change, or an uncertainty estimate. As a result, the posted information does not show whether the score increased or decreased, how large any observed change was, or how variable the measurements were. It is not possible to judge the precision of the primary result from the registry record. The stated hypothesis about temperature and sympathetic nervous system activity is a rationale, not a reported result.

Even with a reported post-treatment result, this study's open-label, single-group design would not establish how outcomes would have differed under a control condition. General interpretation of uncontrolled pre-post observations must account for possible influences other than the intervention. The registry record does not include a comparator result or report methods that could resolve this limitation.

The safety entries report zero serious and zero other events for each displayed treatment group label, while death counts are not reported. These entries should be read as the recorded event counts, not as proof that no risk exists. The record does not report the details needed to interpret the safety follow-up more fully.

Accordingly, the defensible conclusion is limited to what the registry documents about the design, intended endpoint, withdrawals, and listed adverse events. The record does not support a conclusion about the magnitude or precision of change in WPI, nor does it establish a causal effect of the device. It also does not confirm the proposed biological mechanism.

13. Why This Trial Matters Statistically

This study illustrates why a trial's design and its posted results need to be read together. The registry identifies a specific clinical endpoint, the Widespread Pain Index, and describes its scale and intended timing. Yet without the observed endpoint value, readers cannot assess the size or precision of the result. A clear outcome definition is important, but it cannot substitute for the outcome data.

The single-group, open-label design also shows the distinction between describing change and attributing change. In general, a before-and-after observation may be informative about what happened among participants who were measured. A concurrent comparison is needed to assess how that observed course differs from an alternative condition. This registry record does not describe a comparator for the primary endpoint, so the design cannot support a randomized treatment contrast.

Missing post-therapy data matter as well. The registry reports withdrawals and the absence of their post-therapy measurements, but not the analysis method or the handling of those values. Statistical conclusions depend not only on the endpoint definition, but also on which observations enter the analysis and how missingness is addressed. The record does not provide those details.

Finally, the listed safety counts demonstrate the importance of reading registry labels in context. The two safety group labels appear alongside a study identified as single-group, and the record does not explain a comparative role for them. Treating them as parallel efficacy arms would overstate what the design records. These points make the trial statistically instructive even though the primary endpoint result itself is not reported: design, missing data, outcome reporting, and uncertainty all shape what can be concluded.

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 study from the registry record is the absence of the primary endpoint result. Although WPI after 4 weeks is identified as the primary measure, the record does not report a score, baseline measurement, change, or uncertainty estimate. As a result, the primary clinical outcome cannot be evaluated.

The design is open-label and single-group, with no control comparison described for the primary endpoint. This restricts causal interpretation because observed outcomes cannot be contrasted with outcomes under a concurrent alternative condition. The registry does not report whether other care or factors during the study were recorded.

The population description notes three withdrawals for personal reasons and missing post-therapy data. The registry does not report the analysis population, the handling of missing measurements, or sensitivity analyses. The effect of missing endpoint data on any estimate therefore cannot be assessed. The record also does not state how adherence to twice-daily use was measured.

Although three outcome measures are listed, only the primary endpoint is described in the available record, and results for the other measures are not reported. Statistical methods, multiplicity procedures, and a sample-size justification are not reported in the registry record. The planning description refers to illustrations based on an observed effect, but those calculations are not the trial's own design justification and should not be read as observed power.

Safety interpretation is limited by the sparse registry description. Serious and other event counts are listed for Treatment Group A and Treatment Group B, but the record does not explain these labels in relation to the single-group design. Death counts, follow-up details, and event surveillance procedures are not reported. These limitations constrain interpretation of both effectiveness and safety from the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Investigation of AVACEN Thermal Exchange System for Fibromyalgia Pain — NCT01619579.
• Registry record last updated 2017-02-01; status last verified 2016-12.
• Results first posted 2015-12-01.
• 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 Phase 2, open-label, single-group study of the AVACEN Thermal Exchange System in people with fibromyalgia. The treatment description specifies twice-daily use for 4 weeks. The primary endpoint is WPI score after 4 weeks, on a scale from 0 to 19, with lower scores described as the better outcome. The registry reports enrollment of 22 and states that three participants withdrew for personal reasons without post-therapy data.

The primary WPI result, other outcome results, analysis methods, and analysis populations are not reported in the registry record. No control comparison is described for the primary endpoint. Safety entries list zero serious events and zero other events for each displayed treatment group label; death counts are not reported. These details describe the posted record but do not establish a treatment effect or the precision of an outcome estimate.