Effect of Ultrasound Guided Laser Ablation Therapy on Symptomatic Benign Thyroid Nodules: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of Ultrasound Guided Laser Ablation Therapy on Symptomatic Benign Thyroid Nodules (NCT04277455), a na na study. The primary outcome is Change in Radiographic Volume of Thyroid Nodule From Baseline at 3, 6 and 12 Months After Laser Ablation.

2. Clinical Question

This question is about change over time in the treated group, not a comparison of laser ablation with another treatment. Without a control group, observed changes cannot by themselves separate the effects of treatment from other explanations, such as natural variation in nodule volume or differences in measurement. The registry describes the study as prospective and intended to assess clinical efficacy, safety, tolerability and symptom impact. Those aims do not establish what the posted results demonstrate: the numerical primary-outcome results are not reported in the registry record.

3. Trial Design

The registry describes a prospective, single-group study of laser ablation for symptomatic benign thyroid nodules. The listed allocation is NA, masking is none, and the model is single group. There is no randomized treatment allocation or like-for-like control arm. Accordingly, the central comparison described by the primary outcome is each treated participant’s post-treatment nodule volume relative to baseline, rather than a difference between independent treatment groups.

The registry lists enrollment of 10 and status as completed. The study description says approximately 20 subjects will undergo treatment, while the enrollment field records 10; the registry does not explain this difference. The primary-outcome population description reports that 9 subjects completed the 12-month study visit and that one patient did not return for that follow-up and was determined to be lost to follow-up. The record does not describe how the primary analysis handled missing follow-up measurements.

The primary outcome is percentage change from baseline volume at 3, 6 and 12 months after laser treatment. The registry lists a mean and full range as the summary approach. Secondary outcomes include pain scores immediately after the procedure and at 3 months, questionnaire-based tolerability, and treatment-related adverse events assessed by CTCAE v4.0. The registry lists 11 outcome measures, but numerical results for the primary endpoint are not reported in the registry record.

The study start date is 2020-10-26, the primary completion date is 2023-09-28, and the status is completed. The record lists phase as NA. It does not report a statistical analysis plan, sample-size justification for the actual study, or details of any interim analyses. A planning illustration based on an observed effect is not the same as the design or analysis actually used in this single-group trial.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: 9 subjects completed the 12-month post-procedure study visit. One patient did not return for the 12-month follow up visit and was determined to be lost to follow-up.

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 Radiographic Volume of Thyroid Nodule From Baseline at 3, 6 and 12 Months After Laser Ablation, measured over 12 months.

The primary endpoint is the percentage change in thyroid-nodule volume from baseline at 3, 6 and 12 months after laser ablation. It is intended to describe how the measured volume of the treated nodule changes over follow-up. A percentage scale expresses change relative to baseline, which can make the amount of change easier to interpret across nodules that began at different volumes. That is a general property of relative measures; the registry does not provide the baseline volumes or the calculation details beyond describing the percentage change.

The registry specifies a mean as the endpoint parameter and full range as the dispersion measure. The mean describes the average outcome across the observations included in an analysis. The full range describes the span from the lowest to the highest observed value; it does not, by itself, show how values are distributed between those endpoints or how precisely the mean is estimated. The numerical mean and range at the stated visits are not reported in the registry record.

Volume is a radiographic measure and is relevant to the study’s stated interest in the effects of treatment on symptomatic benign nodules. It is not itself a direct measure of pain, tolerability, or quality of life. The registry lists symptom and tolerability outcomes separately, including pain scores and questionnaire assessments. No inference about those outcomes should be substituted for the missing primary volume results. The record also does not report the imaging measurement procedures or any assessment of measurement reproducibility.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main statistical issue is that the study has one treatment group and measures nodule volume over time. The primary outcome is a percentage change from baseline at 3, 6 and 12 months. In a repeated-measure setting, each follow-up value is naturally interpreted in relation to the participant’s own baseline measurement. This describes within-participant change. It is different from a randomized comparison, which estimates how outcomes differ between treatment groups under the study conditions.

What does a mean percentage change describe?

As a general statistical concept, a mean summarizes the central tendency of a set of values. Here the registry identifies the mean as the primary endpoint parameter, but does not report the actual mean results. A mean can be influenced by unusually large or small observations, particularly in small studies. The registry’s full-range dispersion measure provides the lowest and highest observed values, but does not show the density of observations, the shape of the distribution, or the uncertainty around the mean. The range can also be sensitive to extreme observations. Because the numerical results are absent, these properties cannot be examined for this study’s observed values.

A percentage change is a relative measure: it expresses change in relation to a baseline value. In general, relative change can help compare changes when starting measurements differ. It also depends on the baseline measurement. Small or imprecise baseline values can make percentages unstable, and measurement error at either baseline or follow-up can affect the calculated change. These are general considerations; baseline volumes, measurement precision, and the details of the calculation are not reported in the registry record.

Why does the single-group design matter?

With no separate comparator, a post-treatment change cannot be interpreted as a treatment effect in the same way as a difference between randomized groups. General explanations for change over time can include natural history, regression toward typical values after an unusually high measurement, measurement variability, and other care received during follow-up. The registry does not report whether these explanations applied. A single-group result can still describe what was observed among participants, but causal attribution is limited without a suitable comparison.

Masking is listed as none. In general, knowledge of treatment or visit timing can affect subjective assessments and, depending on procedures, outcome measurement. Nodule volume is radiographic, but the registry does not describe who assessed images, whether assessments were blinded, or whether measurements were independently checked. The lack of these details means the potential for measurement-related bias cannot be evaluated from the record.

What does the planning illustration mean?

The registry includes a sample-size planning description based on an observed effect. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Those are planning assumptions, not results from this trial and not evidence of the trial’s power. The actual trial is listed as single group, so a hypothetical equal-allocation, two-arm planning calculation does not describe its observed design. No numerical planning estimates are reported in the registry record. Sample-size planning illustrations are not observed power, and they should not be treated as proof that the study was adequately sized for its actual analysis.

What can confidence intervals and tests contribute?

In general, a confidence interval shows a range of values compatible with an estimate under the assumptions of the statistical method. Its width helps communicate precision. A hypothesis test addresses compatibility with a specified null model; a p-value is not the probability that a treatment works, nor does it convey the size or clinical importance of an effect. The registry does not report confidence intervals, p-values, or a primary-outcome test. Therefore, neither precision nor statistical evidence for a change can be assessed from the posted results.

Repeated assessments across 3, 6 and 12 months also raise general analysis questions. One could report each visit separately, estimate a trajectory, or use a repeated-measures model that accounts for within-person correlation. These approaches answer somewhat different questions and rely on different assumptions. The registry does not report which approach was used, whether comparisons across visits were planned, or how correlations between repeated measurements were handled. No particular method should be imputed from the endpoint description alone.

Why can over-dispersion matter?

For outcomes that are counts, a statistical model may assume a particular relationship between the average count and its variability. Over-dispersion occurs when observed variability exceeds that assumption; ignoring it can make uncertainty estimates too small. This is a general issue for count outcomes, such as event counts, and is not the principal form of the registered continuous volume endpoint. The registry does not report a count-model analysis or any model for adverse events. With the available event summaries, no model-based comparative estimate can be reconstructed.

Finally, analysis choices depend on the population included. The record reports 9 subjects completing the 12-month visit and one patient lost to follow-up, but does not identify an intention-to-treat population, a per-protocol population, or another analysis set. It also does not report whether missing observations were imputed or whether analyses used only observed measurements. Those details affect how estimates are interpreted and cannot be recovered from the completion count alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary volume outcome and secondary measures of pain, tolerability, and treatment-related adverse events. When a study examines several outcomes or several time points, there are general statistical concerns about multiplicity: the more questions tested, the greater the chance that at least one result may appear statistically notable by chance. A prespecified hierarchy, adjustment, or clear distinction between primary and exploratory analyses can help readers interpret multiple tests. The registry does not report a multiplicity strategy, a statistical analysis plan, or which outcomes were formally tested.

The record lists zero analyses. It gives the primary endpoint’s measurement schedule and summary description, but no numerical primary-outcome results, confidence intervals, or test statistics. The study is completed, yet the record does not report whether results were unavailable, not analyzed, or omitted from the registry entry. These possibilities should not be guessed.

Missing data are relevant because the primary-outcome description says 9 subjects completed the 12-month visit and one patient did not return and was determined to be lost to follow-up. The record does not report the handling of that missing visit, whether there were missing observations at earlier visits, or whether a sensitivity analysis was conducted. In general, results from participants with observed follow-up may be affected if the reasons for missingness are related to outcomes. This is a methodological possibility, not a claim about the participant who was lost to follow-up.

The registry does not name an analysis population or specify an intention-to-treat, per-protocol, or complete-case approach. It also does not state whether baseline measurements were available for every participant or how volume measurements were quality-checked. As a result, the analysis population and missing-data assumptions cannot be evaluated from the 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 non-serious adverse event terms

The registry reports that 10 participants were at risk for serious adverse events and 0 were affected; it reports 10 at risk for other adverse events and 10 affected. It also reports 0 deaths. These are counts in the treatment arm, not rates calculated against a comparator, and no comparative safety effect can be estimated from a single-group record.

The registry lists treatment-related adverse events assessed by CTCAE v4.0 as a secondary outcome. However, it does not provide serious adverse event terms, and the serious-event term list is empty. The entry for other adverse events does not identify event types, severity, timing, duration, recurrence, or whether each event was considered related to treatment. The record’s outcome wording and its adverse-event summary should therefore be read as separate registry descriptions; the summary alone does not answer every detail of the planned safety assessment.

Zero reported serious events is a count, not proof that the risk of serious events is zero. In general, small studies have limited ability to characterize uncommon harms, and a single-group study cannot compare event frequencies with an untreated or alternative-treatment group. The reported counts are descriptive. They do not establish that treatment is safe or unsafe, and they should not be interpreted as medical advice.

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

The registry describes a prospective study of ultrasound-guided laser ablation for symptomatic benign thyroid nodules, with radiographic volume change as the primary outcome and follow-up at 3, 6 and 12 months. It also records pain, tolerability, and adverse-event outcomes. This information clarifies the study question and the types of outcomes the investigators intended to assess.

What the record does not establish is the magnitude of the primary outcome. Numerical results for percentage volume change and its full range are not reported in the registry record. There are also no reported confidence intervals or hypothesis-test results for that endpoint. Thus, neither the direction and size of the measured change nor its statistical precision can be described. The study’s completed status is not a substitute for outcome estimates.

The single-group design also limits causal interpretation. Even if a before-and-after volume change were available, it would describe change among treated participants, not the difference between laser ablation and a control treatment. General influences on change over time and measurement cannot be separated from a treatment effect without an appropriate comparison. This limitation does not mean that the treatment had no effect; it means that the design does not isolate a comparative effect.

The record reports follow-up completion for the primary endpoint and a loss to follow-up, but does not explain how missing data were handled. The safety summary records serious and other adverse events and deaths, but provides limited event detail and no comparison group. Consequently, the evidence in the registry record is insufficient to quantify efficacy, precision, or comparative safety. It supports a description of the study and its reported counts, not a conclusion that treatment does or does not work.

13. Why This Trial Matters Statistically

This trial is statistically notable because it makes the distinction between an outcome question and an answer to that question especially clear. The registry defines a measurable primary endpoint—percentage change in nodule volume from baseline—and specifies follow-up at 3, 6 and 12 months. But it does not report the numerical endpoint results. A clearly described outcome cannot be interpreted quantitatively without its estimates and information about their uncertainty.

The single-group structure is equally important. A change from baseline can be useful as a descriptive summary, but it is not equivalent to a controlled treatment effect. Readers need to know whether the question is “what changed after treatment?” or “what changed because of treatment compared with an alternative?” The registry design addresses the former more directly than the latter. This is a general lesson in interpreting prospective studies, not a judgment about the clinical value of the study.

The record also illustrates why follow-up and analysis populations should be reported together. It notes that 9 subjects completed the 12-month visit and one patient was lost to follow-up, yet does not describe the analysis set or missing-data handling. Those details help readers understand exactly which observations contribute to an estimate and what assumptions are needed to interpret it.

Finally, the safety counts show why descriptive event summaries should not be mistaken for a complete safety comparison. Event counts without event terms, comparative data, or precision estimates have limited interpretive reach. Taken together, the study record highlights the importance of publishing numerical outcome results, analysis methods, missing-data decisions, and event details alongside trial status and endpoint descriptions.

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 the primary outcome is that numerical volume-change results are not reported in the registry record. The mean and full range are named as summary measures, but their values at 3, 6 and 12 months are absent. There is therefore no estimate to assess for magnitude or variability, and no interval estimate to describe precision.

The study is single group, with no randomized comparator, and masking is listed as none. This limits causal attribution and leaves the possibility of time-related or measurement-related explanations for any observed change. The registry does not report image-reading procedures, assessor masking, reproducibility checks, or details of volume measurement. These are unreported methods, not evidence that measurement was unreliable.

Follow-up is incomplete for the 12-month visit: the record reports 9 completers and one patient lost to follow-up. The handling of missing data, the analysis population, and the availability of measurements at earlier visits are not reported. The record also does not explain the difference between the enrollment field of 10 and the study description’s estimate of approximately 20 subjects. No conclusion about the reason for that difference is warranted.

The record lists 11 outcome measures but does not provide a statistical analysis plan, multiplicity approach, or numerical analyses. The safety summary provides counts but no serious-event terms and limited detail about other adverse events. The study’s completed status and stated objectives do not resolve these reporting limitations.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effect of Ultrasound Guided Laser Ablation Therapy on Symptomatic Benign Thyroid Nodules — NCT04277455.
• Registry record last updated 2024-06-03; status last verified 2024-05.
• Results first posted 2024-06-03.
• 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

NCT04277455 is a completed, prospective, single-group study of ultrasound-guided laser ablation for symptomatic benign thyroid nodules. The registry lists enrollment of 10, no masking, and no separate comparator. The primary endpoint is percentage change in radiographic nodule volume from baseline at 3, 6 and 12 months, summarized by a mean and full range.

The primary-outcome description reports 9 subjects completing the 12-month visit and one patient lost to follow-up. Numerical primary-outcome results, confidence intervals, analysis methods, and missing-data handling are not reported in the registry record. Safety entries report 0 serious adverse events, 10 participants affected by other adverse events, and 0 deaths. These descriptive entries do not provide a comparative safety estimate.

The record describes the study question and follow-up, but does not permit quantitative assessment of the primary result or its precision.