The Qutenza Patch as Treatment for Disabling Treprostinil (Remodulin) Infusion Site Pain: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for The Qutenza Patch as Treatment for Disabling Treprostinil (Remodulin) Infusion Site Pain (NCT01260454), a na phase 2 study. The primary outcome is Pain Score on a Visual Analogue Scale.

2. Clinical Question

3. Trial Design

This completed Phase 2 study evaluated Qutenza for pain associated with new subcutaneous treprostinil infusion sites. The sponsor was the University of Rochester. The registry record gives a start of 2010-11 and primary completion of 2011-12. Enrollment was 6. The study population was associated with pulmonary hypertension and pulmonary arterial hypertension.

The design was single-group, with no allocation to a separate comparator condition. All participants were actively treated with Qutenza, and masking was none. The study was described as open-label and unblinded: participants and study personnel were not masked to treatment. The registry summary says participants would use a pain diary tool with which they were already comfortable. That approach allowed repeated symptom recording after a new infusion site was placed, but the absence of masking and a concurrent comparator limits what can be separated from expectations, natural changes in pain, or other influences over time.

The intervention was the Qutenza 8% capsaicin patch. The registry rationale notes that treprostinil can irritate skin and that infusion-site pain may be intense during the first 7-10 days after a new site is placed. Investigators hypothesized that pretreatment of the skin would reduce pain intensity and duration. These statements describe the rationale and hypothesis, not a reported finding.

The primary outcome was a mean of daily maximum visual analogue pain scores over the period after a new infusion site. A secondary outcome concerned the number of participants experiencing a pain level greater than 6 on the 10-point visual analogue score; another concerned participants who used narcotics following a site change. Numerical results for these outcomes are not reported in the registry record. The record also does not report a detailed statistical analysis plan or a sample-size justification for the study.

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: Of the 26 screened 10 had a pain score \> or = 6 on two consecutive days. 6 of these 10 agreed to enroll.

Overall Study

Analysis population for the primary outcome, as defined in the registry: One subject did not meet the inclusion criteria and was excluded from the efficacy analysis.

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 Pain Score on a Visual Analogue Scale, measured over 14 days after a new infusion site.

The primary endpoint was the average of participants’ daily maximum pain-intensity scores after placement of a new infusion site. Participants were to record the maximum pain they experienced each day on a 0-10 visual analogue scale. Recording continued for 14 days unless a participant recorded 0 for two consecutive days. The endpoint was defined as the sum of the daily maximum scores divided by the number of days recorded, generally 14, with a possible range of 0-10.

This endpoint reduces a series of diary entries to a single summary of pain intensity over the specified follow-up period. Using each day’s maximum focuses on the most intense pain reported that day, while averaging across recorded days represents the overall level of those daily maxima during follow-up. It does not, by itself, describe the full pattern of pain, such as when pain peaked or how scores changed from day to day. The separate secondary outcome addressing pain duration was intended to capture a different aspect of the experience, but the registry record does not define or report a numerical duration result.

The registry record says that one subject did not meet the inclusion criteria and was excluded from the efficacy analysis. It does not report the numerical primary endpoint mean or its standard deviation. Consequently, the endpoint definition is available, but the posted registry record does not permit an assessment of the observed average pain score or its variability.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

A continuous endpoint, such as the average of visual analogue pain scores, is commonly described using a mean and a measure of variability. The mean gives a central summary of the recorded values. The standard deviation describes how spread out those values are around the mean. These summaries answer different questions: the mean describes the average level, while the standard deviation describes variation among observations. Neither is reported numerically for this study’s primary endpoint in the registry record.

A confidence interval is a general statistical tool for expressing uncertainty around an estimated quantity. It gives a range of values compatible with the data and the method used, rather than guaranteeing that the true value lies within the interval. A narrow interval indicates greater precision than a wide interval under the same method. The registry record does not report a confidence interval for the primary endpoint, so the precision of the estimate cannot be evaluated from the record.

A p-value is another general statistical measure. In a specified hypothesis test, it describes how incompatible the observed data are with a null hypothesis, assuming the model and test assumptions hold. It is not the probability that a treatment works, nor does it measure the size or practical importance of an effect. The registry record does not report a p-value or identify a test for the primary outcome. No significance conclusion can therefore be drawn from a test result in the record.

In a controlled comparison, an estimated difference between groups can address whether outcomes differed between the assigned conditions, subject to the design and analysis. Here, the study is single-group and has no separate comparator. A within-group score or change, even if reported, would describe the observed participants but could not isolate a treatment effect in the way a randomized between-group comparison is intended to do. The record reports no numerical outcome with which to make even that descriptive assessment.

The pain diary produces repeated observations over time. The registry’s primary endpoint compresses those observations into the average of daily maximum scores, using the available recording days and generally 14 days of scores, unless the stated stopping condition is met. Averaging can provide a concise summary, but it can obscure the trajectory: different patterns of daily pain can yield similar averages. The secondary outcome concerning pain level greater than 6 addresses a thresholded aspect of pain, while the narcotic-use outcome records a separate participant-level measure. The record does not report numerical results for either secondary outcome.

General statistical methods for repeated measurements can account for the dependence among observations from the same participant. Whether a model of that kind was used, or whether the endpoint was analyzed only as a participant-level average, is not reported in the registry record. The record also does not report the statistical test, model specifications, adjustment variables, handling of ties or outlying scores, or the approach to incomplete diary data. These details matter because different analysis choices can affect estimates and their uncertainty.

The registry lists one subject as excluded from the efficacy analysis for not meeting inclusion criteria. That is an analysis-population detail, but the record does not describe any further exclusions or whether all other recorded diaries were complete. It does not report an imputation method or a sensitivity analysis for missing observations. General missing-data methods make assumptions about why values are absent and how the missingness relates to observed or unobserved outcomes; without the study’s handling details, those assumptions cannot be assessed.

The sample-size material is described as a planning illustration based on the observed effect, not as the trial’s own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. These are planning assumptions, not evidence that this single-group study had a prespecified two-arm design. A projected sample size is not observed power. Observed power is not a substitute for reporting the estimated outcome and its uncertainty, and a planning illustration does not establish that the study was adequately sized.

Over-dispersion is a general issue when data vary more than a chosen statistical model expects. If a model underestimates variability, its uncertainty estimates can be too small and its intervals or tests can be misleading. The primary endpoint is continuous, and the registry record does not describe a model or variance assumption that would permit a study-specific assessment of over-dispersion. More generally, statistical methods should match the outcome and data structure; the registry record does not report enough detail to evaluate that match.

Multiplicity is the general concern that conducting several statistical tests can increase the chance of at least one apparently notable result. This record lists a primary pain score and secondary outcomes, but does not report a testing hierarchy, adjustment for multiple comparisons, or the number of outcome tests actually performed. It would therefore be inappropriate to assume either that multiplicity was adjusted for or that it was ignored in the analysis. The registry record does not provide the analysis detail needed to determine this.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Qutenza Patch")
n   <- c(5)
m   <- c(2.89)
sp  <- c(0.71)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Qutenza Patch  5  2.890  0.710  2.008  3.772

11. Multiplicity, Missing Data and Analysis Populations

The registry record identifies a primary outcome and secondary outcomes. The primary outcome is the average of daily maximum pain scores. The secondary outcomes concern the number of participants with a pain level greater than 6 on the 10-point visual analogue score and the number who used narcotics following a treprostinil infusion-site change. The record does not report a multiplicity strategy, such as a prespecified hierarchy or adjustment across outcome tests. It also does not state how many tests were conducted or which outcome tests were considered confirmatory.

The diary instructions specified recording a daily maximum for 14 days, unless scores of 0 were recorded for two consecutive days. This defines a stopping condition for recording; it does not explain how missing diary entries were treated. The registry record does not report the amount or pattern of missing diary data, whether participants with incomplete diaries were included, or whether any imputation or sensitivity analysis was used. General methods for missing data depend on assumptions about why observations are absent, so the absence of these details limits assessment of potential bias.

The record states that one subject did not meet the inclusion criteria and was excluded from the efficacy analysis. It does not provide further detail about the efficacy analysis population or describe an intention-to-treat analysis. No statistical analysis plan is reported in the registry record, so the planned handling of missing data, exclusions, and multiple outcomes cannot be compared with the analysis ultimately conducted.

12. 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 5% reporting threshold.

Most frequent non-serious adverse event terms

The registry lists 6 participants at risk for serious adverse events and 0 participants affected by serious adverse events in the Qutenza Patch group. For other adverse events, it lists 6 at risk and 4 affected. These are participant counts in the registry’s event categories; they do not indicate how many events each affected participant experienced.

The serious adverse event count and the other adverse event count are separate summaries. The listed 0 serious-event count does not mean that no other adverse events occurred: the registry separately records 4 participants affected by other adverse events. No serious adverse event terms are listed. The deaths field has no numerical value, so deaths are not reported in the registry record rather than established as zero.

These figures are descriptive. They do not establish whether an event was caused by Qutenza, and the registry record does not provide event details that would support a more specific interpretation. With enrollment of 6, the safety counts also describe a small study population and cannot, by themselves, characterize uncommon risks.

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

This study is relevant as an early clinical evaluation of Qutenza pretreatment for pain associated with a new subcutaneous treprostinil infusion site. It records a specific clinical rationale, an open-label single-group design, and a diary-based primary endpoint focused on daily maximum pain intensity. Those design details clarify what the investigators intended to measure.

However, the registry record does not report the numerical primary pain result or the numerical secondary-outcome results. There is therefore no reported estimate to interpret for average pain intensity, and no confidence interval or other measure of precision is reported. The registry record cannot establish from the posted outcome information whether scores were lower, how large any change might have been, or how consistently participants’ experiences varied.

Even if a within-group result were available, a single-group design would not provide a concurrent comparison for distinguishing treatment-associated changes from other explanations. The open-label, unblinded approach also means that participants and study personnel knew the intervention was being given. For a self-reported symptom recorded in a diary, that knowledge is relevant when considering possible influences on reporting. These are design considerations, not proof that any particular bias occurred.

The enrollment and efficacy-population information also warrant care: the registry lists enrollment of 6 and states that one subject was excluded from the efficacy analysis for not meeting inclusion criteria. Further details about missing diary entries and the analysis population are not reported. Safety counts are available, but they are descriptive and do not establish causality.

The result should therefore be understood as an incompletely reported record of a small exploratory study, not as a quantitative estimate of treatment effect. The record supports description of the question, intervention, design, and endpoint, but it does not support a conclusion about the magnitude or precision of pain outcomes.

14. Why This Trial Matters Statistically

Statistically, this study illustrates the distinction between defining an outcome and reporting its result. The registry record specifies how daily maximum pain scores were to be recorded and averaged, including the 0-10 scale, the 14-day period, and the stopping condition. That definition helps readers understand what the primary endpoint represents. Without its numerical result and variability, however, the endpoint cannot be evaluated as an estimate.

The design also makes the comparison question important. A single-group study can describe outcomes among participants who receive an intervention, but it does not include a concurrent group to help distinguish an intervention-associated pattern from other changes. Open-label, unblinded measurement is another consideration for a diary-based symptom outcome. Neither feature proves that a result would be biased; both affect what a result could support.

The registry’s sample-size material is explicitly a planning illustration based on the observed effect, rather than the study’s own design. It uses assumptions for a hypothetical two-arm calculation, while the actual study is single-group. This is a useful distinction in statistical reporting: a planning calculation is not a description of the trial’s design, and it is not observed power. The record does not report a sample-size justification for the study itself.

Finally, the exclusion from the efficacy analysis, the absence of reported missing-data methods, and the lack of numerical efficacy outcomes show why population definitions and analysis details matter alongside an endpoint definition. A clear result requires enough information to understand who contributed data, how observations were handled, and how uncertain the estimate is. Those elements are not reported in the registry record.

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 central limitation for interpreting efficacy is that the registry record does not report numerical primary or secondary outcome results. The primary endpoint is defined, but no mean, standard deviation, confidence interval, or test result is reported. The observed level and variability of pain therefore cannot be assessed from the registry record.

The single-group design has no concurrent comparator, and allocation is listed as not applicable. The study was open-label and unblinded. These design features limit the ability to separate changes over time or reporting influences from an intervention-associated pattern. They do not establish that bias occurred, but they constrain causal interpretation.

Enrollment was 6, and the record says one subject did not meet inclusion criteria and was excluded from the efficacy analysis. The registry does not give further details about the efficacy population, completeness of the diaries, handling of missing observations, or sensitivity analyses. It also does not report a statistical analysis plan, multiplicity approach, or sample-size justification for the study.

The endpoint summarizes daily maximum scores across the recording period. As a general limitation of averaging repeated observations, a single mean can conceal changes in the timing or pattern of symptoms. The registry record does not report daily score trajectories or a numerical outcome summary that would allow those patterns to be examined.

The safety figures are also limited to participant counts in broad categories. Serious adverse event terms are not listed, and deaths are not reported as a numerical result. The record does not provide details sufficient to assess event timing, severity beyond the category, or attribution.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: The Qutenza Patch as Treatment for Disabling Treprostinil (Remodulin) Infusion Site Pain — NCT01260454.
• Registry record last updated 2016-04-21; status last verified 2016-03.
• Results first posted 2016-02-22.
• 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

The registry record describes a completed Phase 2, open-label, unblinded, single-group study sponsored by the University of Rochester. It lists enrollment of 6 and evaluates Qutenza, an 8% capsaicin patch, as pretreatment for pain after a new subcutaneous treprostinil infusion site. The primary outcome is the average of daily maximum visual analogue pain scores recorded over 14 days, subject to the stated stopping condition. One subject did not meet inclusion criteria and was excluded from the efficacy analysis.

The record does not report numerical primary or secondary efficacy results, a confidence interval, or the detailed statistical analysis plan. It lists 0 participants affected by serious adverse events and 4 affected by other adverse events, among 6 at risk for each category. Serious event terms are not listed, and deaths are not reported numerically.