Trial Comparing PLA to HIGRT (PROVE-HCC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial Comparing PLA to HIGRT (PROVE-HCC) (NCT03402607), a randomized na study. The primary outcome is Change in Quality of Life (QOL) Using EORTC C-30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30).

2. Clinical Question

The trial focused on quality of life rather than a tumor-control or survival endpoint. Its primary measure was the EORTC C-30 summary score, calculated from 13 of the 15 questionnaire scales. The registry states that lower summary scores indicate better quality of life. The outcome population was participants with measurements at both baseline and the one-month time point, so the endpoint results do not represent every enrolled participant.

The arm-level means were -6.25 for PLA and -10.0 for HIGRT. These are changes in score, not scores at a single visit. The registry reports a 95% confidence interval for each arm's mean change, but does not report a direct estimate or inferential test of the difference between arms. The clinical question is therefore only partly answered by the posted primary results: they describe within-arm changes among participants with paired measurements, without establishing whether the arms differ.

3. Trial Design

This was a randomized, parallel-arm phase II trial comparing PLA with HIGRT in people with hepatocellular carcinoma who were not surgical candidates or declined surgery. The registry lists the phase as NA. It identifies Duke University as the sponsor, gives a planned enrollment of 12, and marks the study as terminated. The registry lists a start date of 2018-08-08 and a primary completion date of 2019-07-25.

The trial had no masking. In an open-label design, participants and study personnel are not masked to the assigned treatment. That feature is important when interpreting a self-reported quality-of-life outcome: awareness of treatment can potentially influence responses, expectations, or how questionnaires are completed. This is a general consideration, not a claim that such influence occurred in this trial.

The registry lists two treatment arms: PLA and HIGRT. The PLA description refers to a probe inserted into the liver tumor with CT and ultrasound guidance, followed by high-frequency current intended to heat the tumor. The HIGRT description refers to external radiation delivered using multiple beams from multiple angles. Its description says treatment typically involves 5-10 treatments and that participants would receive between 5-10 fractions.

The primary outcome was the change in EORTC C-30 summary score from baseline to one month. The posted arm-level endpoint data include 4 participants in the PLA arm and 5 in the HIGRT arm. These counts are smaller than the planned enrollment of 12, and the primary outcome population is specified as participants who completed the questionnaire at both time points. The registry does not report why some enrolled participants are not represented in these endpoint counts.

The registry also lists secondary outcomes involving other quality-of-life measures, adverse events, and healthcare-system costs. No statistical analysis results are listed for an inferential comparison. The protocol details, including the allocation procedure, the rationale for the planned enrollment, and any interim analyses, 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: Participants who completed the EORTC C-30 at both time points.

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 Change in Quality of Life (QOL) Using EORTC C-30 (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30), measured over Baseline to one month.

The primary endpoint is change in quality of life measured with the EORTC C-30 from baseline to one month. The registry describes a summary score calculated from the mean of 13 of the questionnaire's 15 scales, excluding the Global Quality of Life scale and the Financial Impact scale. It states that 28 items range from 1 (not at all) to 4 (very much), while two range from 1 (very poor) to 7 (excellent). The total summary score ranges from 30 to 126, with lower scores indicating better quality of life. Only the change in summary score is reported; individual subscale scores are not reported.

Quality of life is a patient-reported outcome: it records participants' own assessments rather than relying solely on clinical observations. A change score compares a participant's follow-up score with their baseline score, making it relevant to a question about how reported quality of life shifts after treatment. As a general statistical point, a change score is not the same as a follow-up score; its interpretation depends on the direction and scale of the measure and on the baseline-to-follow-up interval.

The registry identifies the primary endpoint population as participants who completed the EORTC C-30 at both time points. This means the posted means describe a subset with paired measurements. The registry does not report the results for individual questionnaire scales or give additional detail about how missing questionnaires were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is continuous: it is a numerical score, and the registry reports a mean change for each arm. A mean is the arithmetic average of participant-level values. In general, it provides a concise description of the center of a distribution, but it does not show how individual participant changes vary. The record does not provide participant-level observations or a spread measure such as a standard deviation.

What do the confidence intervals describe?

The registry gives a 95% confidence interval for each arm's mean change. In general, a confidence interval expresses the precision of an estimate under the assumptions of the method used to construct it. It is not a range containing 95% of individual participants' changes, and it does not mean that the probability the fixed true value lies in this particular interval is 95%. The values reported for PLA are -14.9 to 2.4; for HIGRT they are -26.21 to 6.21. Both intervals include zero, and both cover changes on either side of zero.

The breadth of an interval depends on factors such as the variability of observations and the amount of information available. In general, fewer observations tend to yield less precise estimates when other conditions are similar. Here the posted primary endpoint counts are 4 and 5, so the mean changes should be read with substantial uncertainty. The registry does not identify the method used to construct the confidence intervals, and further details of the statistical analysis are not reported in the registry record.

Why is an arm comparison different from two arm summaries?

A comparative randomized trial asks whether outcomes differ between assigned treatments. Separate arm means describe each group, but a direct treatment comparison ordinarily requires an estimated contrast between arms and its uncertainty. The registry reports neither a contrast nor an inferential test for this endpoint. The fact that the means are different numerically does not, by itself, establish a treatment difference. Likewise, confidence intervals calculated separately for each arm are not a substitute for a confidence interval for the between-arm contrast.

Random assignment is intended, in general, to support comparisons by balancing prognostic factors across treatment groups on average. It does not guarantee balance in a small realized sample. The registry identifies the design as randomized, but the allocation method and any adjustment variables are not reported in the registry record. No adjustment model or analysis population beyond participants completing the measure at both time points is specified in the posted endpoint description.

What does the change score represent?

The outcome is change from baseline to one month. A change score represents the difference between a participant's follow-up and baseline measurement, and the arm mean summarizes those participant-level changes. The measure's scale runs from 30 to 126, with lower scores indicating better quality of life. Consequently, a negative mean change indicates a decrease in the score, but interpretation should remain tied to the scale's direction and the interval measured. The reported change is not an absolute quality-of-life level at one month. Baseline means and follow-up means are not reported, nor are individual scale results.

As a general matter, analysis of change scores can be affected by baseline differences and measurement variability. Other analysis approaches may model follow-up while accounting for baseline, but whether such an approach was planned or used is not reported in the registry record. No analytic method should be assumed beyond the posted arm-level means and confidence intervals.

How should planning calculations be understood?

Any sample-size figures associated with an observed effect are planning illustrations, not observed power. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. In general, such calculations answer a hypothetical planning question: how many participants per arm might be needed under specified assumptions to detect an effect of a chosen size. They do not show the probability that this completed trial detected an effect, and they do not change the uncertainty in the observed results.

The registry's own sample-size justification is not reported in the registry record. The record also does not report whether any interim analyses were planned or conducted, which multiplicity procedure was specified, or the detailed method for handling missing outcome data. These absences matter because they limit assessment of whether the posted results follow a prespecified statistical plan.

More generally, small studies can produce unstable estimates and wide intervals, especially when outcomes vary among participants. This is a statistical limitation rather than evidence that the treatment effects are necessarily large, small, or absent. The appropriate emphasis is on the size and uncertainty of the posted estimates and on the missing direct comparison, not on a binary interpretation of statistical significance.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 secondary outcomes, including quality-of-life measures, adverse events, and healthcare-system costs. It lists 6 outcome measures in total. Multiple outcomes create a general statistical issue: when many hypotheses are tested, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for multiplicity. The registry does not report a multiplicity adjustment, a hierarchy of outcomes, or which secondary outcomes were intended to be confirmatory. Since no inferential analyses are posted, the record does not show how multiplicity was handled in analysis.

The primary outcome population is defined as participants who completed the EORTC C-30 at both baseline and one month. The reported endpoint counts are 4 for PLA and 5 for HIGRT. The registry does not report the amount or reasons for missing questionnaire data, the number of participants who began but did not complete the measure, or a method for handling missing values. It also does not report whether participants were analyzed according to randomized assignment regardless of treatment received, or describe another analysis population.

In general, analyzing only participants with measurements at both time points can yield a different result from analyzing all randomized participants, particularly if completion is related to health, treatment experience, or outcome. That is a general concern, not evidence that missingness was related to outcome in this trial. Without information about missingness or sensitivity analyses, the potential impact cannot be assessed.

The registry does not report a protocol-defined statistical analysis plan, any interim analyses, or details of the randomization process. These details are not reported in the registry record, so the posted results cannot be checked against an analysis plan from the available record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalization (33.3%).

The registry reports serious adverse event counts for 6 participants at risk in each arm. In the PLA group, 2 serious adverse events are reported; in the HIGRT group, 1 is reported. The registry reports 0 deaths in each group. These are counts of events or participants as presented in the adverse-event record; the registry does not clarify in the information whether a participant could contribute more than one event to a count.

For other adverse events, 0 are reported in the PLA group and 1 in the HIGRT group, with 6 participants at risk in each arm. The record lists Hospitalization, 33.3%, among the top serious adverse event terms. It does not provide further detail about the event's distribution by arm in that term listing, so it should not be assigned to a particular arm based on the information reported.

In general, adverse-event counts in a small study are descriptive and do not provide a precise estimate of comparative risk. The number at risk is small, and the registry does not report a statistical comparison of safety outcomes. These figures should not be treated as proof that one treatment is safer or less safe. The record also does not provide further event-level details, timing, duration, or severity grading beyond the listed serious-event information.

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

The primary outcome results describe average changes in EORTC C-30 summary score among participants with measurements at baseline and one month. The reported mean change is -6.25 for PLA and -10.0 for HIGRT. Since lower scores indicate better quality of life, both arm means reflect a decrease in the score. The confidence intervals are broad and each includes zero, so the estimates are imprecise and compatible with a range of possible mean changes.

The results do not establish that the treatments differ. The registry does not report a between-arm estimate, confidence interval for a difference, p-value, or inferential analysis. Nor do the within-arm changes by themselves show that either treatment caused a change: without a suitable comparison, observed changes can reflect treatment, the passage of time, other influences, or measurement variation. These are general interpretive considerations, not conclusions about what occurred in this trial.

The results also do not describe the full quality-of-life profile. The registry reports only the change in summary score and no individual subscale scores. The summary is based on 13 of 15 scales and excludes the Global Quality of Life and Financial Impact scales. It therefore does not capture every dimension represented in the questionnaire.

The trial's randomized design is relevant to comparative interpretation, but the primary endpoint data come from 4 PLA participants and 5 HIGRT participants, out of planned enrollment of 12. The reason for the difference between planned enrollment and the endpoint counts is not reported in the registry record. The small endpoint groups and missing information about completion and analysis make the results uncertain and limit their generalizability.

The record does not report why the trial was terminated. Termination status alone does not explain the reason or establish anything about the outcome. Taken together, the posted results provide descriptive, preliminary information about arm-specific score changes, not a conclusive test of comparative quality-of-life effects or a basis for medical advice.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combines a randomized two-arm design with a patient-reported continuous outcome, while posting only arm-specific summaries for the primary endpoint. Randomization can support a treatment comparison in principle, but the central comparative quantity is the difference between arms and its uncertainty. Since the registry does not report that quantity or an inferential test, readers cannot use the posted primary results to assess the precision of the treatment contrast directly.

The endpoint counts also illustrate the importance of distinguishing planned enrollment from the population contributing data to an outcome. Planned enrollment was 12, while the primary outcome is reported for 4 PLA participants and 5 HIGRT participants. The registry defines the endpoint population by completion at both time points but does not explain why the remaining enrolled participants are not represented. This limits assessment of potential selection from incomplete outcome data.

The broad confidence intervals emphasize that point estimates alone can be misleading. A mean change gives a compact summary, but uncertainty is central to interpretation, particularly with few observations. The intervals allow a range of plausible mean changes and do not establish a direct comparison. A result's numerical direction is not equivalent to evidence that treatment assignment caused a change.

Finally, the listed secondary outcomes raise questions about multiplicity and analysis planning. The registry does not report a prespecified hierarchy, adjustment procedure, or detailed statistical plan. These limitations matter when assessing a terminated trial with a small endpoint population and no posted inferential analysis. The record is useful for understanding what was studied and what descriptive results were posted, while also showing how much comparative interpretation depends on a clearly reported analysis.

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 primary outcome is reported for 4 participants in the PLA arm and 5 in the HIGRT arm, although planned enrollment was 12. The registry does not explain why fewer participants contribute endpoint data, describe the amount or pattern of missing questionnaires, or report sensitivity analyses. As the endpoint population requires completion at both time points, the posted estimates may not represent all randomized participants.

The primary results consist of arm-level mean changes and confidence intervals. A between-arm estimate and inferential test are not reported. The method used to calculate the confidence intervals is also not reported in the registry record. Without a direct comparative estimate, the results do not quantify the uncertainty around the randomized treatment contrast.

The trial is listed as terminated, but the reason is not reported. The statistical analysis plan, rationale for planned enrollment, randomization procedure, and any interim analyses are not reported in the registry record. The registry also does not report an approach to multiplicity despite listing secondary outcomes.

The trial was not masked, and the primary outcome is self-reported quality of life. In general, lack of masking can matter for participant-reported outcomes; the available record does not establish whether it affected responses. Only the summary score change is reported, with no individual subscale results or baseline and follow-up scores. Finally, the registry's small endpoint groups and broad confidence intervals limit the precision of the descriptive estimates and the strength of conclusions that can be drawn.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trial Comparing PLA to HIGRT (PROVE-HCC) — NCT03402607.
• Registry record last updated 2022-07-08; status last verified 2022-07.
• Results first posted 2021-12-06.
• 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

NCT03402607 is a randomized, open-label, parallel phase II trial sponsored by Duke University, comparing PLA with HIGRT for people with hepatocellular carcinoma who were not surgical candidates or declined surgery. The registry lists planned enrollment of 12, status as terminated, a start date of 2018-08-08, and primary completion on 2019-07-25.

The primary outcome was change in EORTC C-30 summary score from baseline to one month. Mean changes were -6.25 among 4 PLA participants and -10.0 among 5 HIGRT participants; both reported 95% confidence intervals include zero. The registry does not report a statistical comparison between arms. It lists secondary outcomes related to other quality-of-life measures, adverse events, and costs. The reason for termination and the detailed analysis plan are not reported in the registry record.