Phase 2 Study of PEG-Intron in Hereditary Hemorrhagic Telangiectasia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Phase 2 Study of PEG-Intron in Hereditary Hemorrhagic Telangiectasia (NCT00588146), a randomized phase 2 study. The primary outcome is Change in Hemoglobin.

2. Clinical Question

These details define the question the study set out to examine, but they do not provide an estimate of the treatment effect. The record does not report a hemoglobin change for either sequence or a statistical comparison between PEG-Intron and standard care. It also does not report an analysis population for the outcome beyond noting that only three subjects completed the study. As a result, the clinical question can be described from the design and endpoint, while the posted outcome information cannot establish the size or precision of any hemoglobin difference.

The crossover structure means participants were assigned to treatment sequences rather than to only one treatment throughout the study. In general, crossover studies can compare responses within the same participant, but interpretation depends on having outcome information across treatment periods and on suitable handling of period and sequence effects. Those details are not reported in the registry record. The stated study purpose includes safety and tolerability; the listed adverse-event counts provide limited descriptive information, not a complete account of comparative safety.

3. Trial Design

This was a Phase 2 randomized, unmasked crossover study sponsored by Mayo Clinic. The registry record lists an enrollment of 10 and a status of terminated. The study start is recorded as 2007-01, and primary completion as 2011-09. The registry record does not state why the study was terminated or provide further information about the circumstances of termination.

Two treatment sequences were described. One sequence received weekly subcutaneous PEG-Intron at 1 microgram/kg/week for 6 months, then standard care for 6 months. The other received standard care for 6 months, then the same PEG-Intron schedule for 6 months. Thus, the planned treatment periods together span one year, matching the primary outcome timeframe of baseline and one year. The record does not report details about how standard care was defined or whether it varied among participants.

Randomization assigns participants to treatment sequences by chance. In a crossover study, each sequence determines the order in which treatments are received. The record specifies random allocation but does not report the allocation procedure, whether sequence assignment was concealed, or whether any stratification was used. Masking is listed as none, so the study was unmasked; further details about who knew treatment assignments are not reported in the registry record.

Only three subjects completed the study. The record explicitly says the numbers were too low to analyze the hemoglobin outcome. Enrollment and completion therefore describe different aspects of participation: enrollment is the number recorded as entering the study, while completion describes those who finished it. The registry record does not report reasons for noncompletion, the number contributing data at each time point, or whether any participants stopped a treatment period but remained under follow-up.

The study lists one outcome measure and zero analyses. It does not report a statistical analysis plan, a sample-size justification, a prespecified interim analysis, or methods for handling incomplete follow-up. The registry record also does not report whether the crossover comparison accounted for treatment sequence, period, or possible carryover. These absences limit assessment of how the planned design was intended to translate into a statistical analysis.

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.

First Intervention (Baseline to 6 mo)

Reasons for not completing this period:

Second Intervention (6 Months to 1 Year)

Analysis population for the primary outcome, as defined in the registry: Only 3 subjects completed the study, so the numbers were too low to analyze the 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 Change in Hemoglobin, measured over baseline, one year.

The primary endpoint was change in hemoglobin, with measurements described at baseline and one year. The registry describes hemoglobin as the amount of hemoglobin in grams per deciliter of whole blood. The unit field itself is not populated, but the endpoint description gives this measurement scale. No numerical hemoglobin values or change estimates are reported.

Hemoglobin is a laboratory measure of the amount of this blood component in a given volume of whole blood. In general, a change endpoint compares a participant’s measurement at a later time with a baseline measurement. It can therefore describe how a measured quantity changes over follow-up, rather than relying only on the final value. That general rationale does not establish what size of change would be important in this study; a threshold for clinical importance is not reported in the registry record.

The selected timeframe aligns with the planned sequence of two 6-month periods. However, the record does not explain whether the primary endpoint was intended to compare the two treatments at one year, describe change over the full study, or use another specific contrast. The primary outcome description states that only three subjects completed the study and that the number was too low to analyze the outcome. Without reported measurements, an effect estimate, or an uncertainty interval, the endpoint cannot be used to quantify a treatment difference from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does randomization contribute?

Randomization assigns participants to treatment sequences by chance. As a general statistical principle, it can reduce systematic differences between groups at the point of assignment, including differences that are measured and differences that are not measured. It does not guarantee balance in a small study, and it cannot correct for outcome data that are unavailable. The registry record identifies the study as randomized but does not describe the randomization procedure or report baseline characteristics by sequence.

How does a crossover design work?

In general, a crossover design assigns participants to sequences in which they receive different treatments in different periods. This study describes PEG-Intron followed by standard care, and standard care followed by PEG-Intron, with each period lasting 6 months. Because participants may contribute observations under both treatments, a crossover analysis can account for within-participant comparisons. Such an analysis also needs to consider period and sequence: outcomes could differ over time, or the order of treatments could matter. A carryover effect is a treatment effect that persists into a later period. These are general design considerations; the registry record does not report whether any of them were addressed in the analysis.

The crossover format also means that the two treatment groups in an adverse-event listing should not automatically be treated as separate sets of people. Participants could be exposed to both interventions in different periods. The registry record does not explain how adverse events were assigned to treatment groups or periods, so the listed group counts should be read as the reported descriptive counts rather than as a fully specified crossover comparison.

What would a confidence interval show?

In general, a confidence interval communicates statistical uncertainty around an estimated effect. A narrow interval indicates greater precision under the analysis assumptions; a wide interval indicates less precision. An interval can also help readers assess which effect sizes remain compatible with the observed data. No confidence interval for the hemoglobin outcome is reported in the registry record. Because there is no reported hemoglobin estimate to accompany such an interval, the primary outcome cannot be interpreted in terms of either effect size or precision.

A p-value, in general, measures how incompatible the observed data are with a specified null model, assuming that model and the analysis assumptions are appropriate. It is not a measure of the probability that a treatment works, nor does it describe the size of an effect. No p-value or other test result for the primary outcome is reported in the registry record. The absence of a test result is consistent with the stated note that the number of completers was too low to analyze the outcome; it should not be converted into a claim that a statistical test was negative.

Why can too few completers matter?

Statistical precision depends on the amount of usable outcome information, not just the number originally enrolled. In general, fewer observations tend to leave more uncertainty around an estimate and may make an analysis unstable. Here, the registry record says that only three subjects completed the study and that this was too few for analysis. It does not report how many had baseline measurements, one-year measurements, or partial data. No estimate of the uncertainty that would have resulted from analyzing incomplete observations is available.

Missing data can also affect what an estimate represents. In general, an analysis of participants with complete measurements may describe a selected subset if completion is related to participant characteristics or outcomes. Methods that use partial data require assumptions about why information is missing. The registry record does not report the amount or pattern of missing data, the reasons for missingness, or any method used to address it. Therefore, readers cannot assess whether any potential analysis would represent all enrolled participants or only those with complete follow-up.

What do the planning assumptions mean?

General sample-size planning asks how many participants would be needed to detect a chosen effect with a chosen level of statistical power under specified assumptions. The registry record describes planning illustrations based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also states that the effect to detect is a stated fraction of the observed effect. These are planning illustrations, not the trial’s own design justification, and they are not observed power. The registry record does not report the trial’s sample-size justification.

For a two-arm planning illustration, equal allocation means planning for the same number of participants in each arm. A two-sided significance level defines how the analysis treats departures in either direction from a null value. A normal approximation uses a mathematical distribution to approximate the sampling behavior of an estimate. These are general meanings of the assumptions, not evidence that the trial used these methods for its primary analysis.

The record does not report a numerical observed hemoglobin effect, and it says that the primary outcome was not analyzed. Accordingly, the planning assumptions do not provide an interpretable treatment estimate or establish what effect the trial was designed to detect. Any sample-size illustration based on an observed effect should be understood as a conditional planning exercise, not as evidence about how likely the study was to find a result. A planning calculation cannot replace the missing outcome analysis.

What can the adverse-event counts establish?

Adverse-event counts are descriptive unless the analysis specifies a comparison, a population, and an appropriate measure of uncertainty. The registry record lists participants at risk and affected counts for serious and other adverse events in each group. It does not report confidence intervals, a statistical test, event timing, or a full event listing. In general, small counts can be particularly sensitive to a change in the observation of a single event. The listed figures should therefore be read as the registry’s recorded counts, not as a precise estimate of relative risk or proof of a treatment difference.

Overall, the methods information permits a description of the planned randomized crossover structure and of general statistical concepts relevant to it. It does not document a completed analysis of the primary endpoint. The record does not report a prespecified statistical analysis plan, interim analyses, an adjustment strategy for multiple tests, or a method for missing data. No unreported method should be assumed.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study makes several statistical comparisons or tests several outcomes. In general, the more tests conducted, the greater the chance that at least one result will appear unusual by chance if each is interpreted separately. The registry record lists one outcome measure, change in hemoglobin, and zero analyses. It does not report a multiplicity adjustment or identify additional planned statistical comparisons. Given that the primary outcome was not analyzed, the record does not provide a set of primary-outcome tests whose multiplicity can be evaluated.

The record says only three subjects completed the study and that the numbers were too low to analyze the hemoglobin outcome. It does not report the amount of missing outcome data, the reasons participants did not complete, or which participants had measurements at baseline or one year. It also does not describe whether participants with partial data were included in any analysis. These details matter because the interpretation of missing-data methods depends on how and why observations are missing.

The analysis population is not reported in the registry record. In general, an intention-to-treat analysis seeks to analyze participants according to their randomized assignment, while other analysis populations may require adherence to treatment or availability of particular measurements. These definitions are not interchangeable, and the record does not state which population was intended for the primary outcome. No method for handling missing observations or deviations from assigned sequence is reported. With no hemoglobin analysis and no specified analysis population, the record cannot show how the randomized design was carried through into the final outcome analysis.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (30.0%).

For serious adverse events, the registry record lists 3 affected among 10 at risk in the PEG-Intron group and 0 affected among 10 at risk in the standard-care group. For other adverse events, it lists 2 affected among 10 at risk in each group. The most frequently listed serious adverse-event term is neutropenia at 30.0%. Death counts are not reported in the registry record.

These are descriptive counts, not a complete statistical comparison. The record does not report confidence intervals, a test of the difference, event timing, or details about severity beyond the serious and other categories. It does not explain whether the affected counts represent unique participants or how events were assigned to treatment periods. Because the study used a crossover design, the same participant could have received both treatments; the registry record does not provide enough detail to reconstruct exposure-specific person-level comparisons.

Accordingly, the counts describe what the registry lists for each group, but do not establish the comparative frequency or cause of adverse events. The record does not provide enough information to interpret the neutropenia listing beyond its reported term and percentage.

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

The registry record establishes that a randomized, unmasked crossover study was conducted to evaluate PEG-Intron in people with severe complications related to HHT. It also records the planned treatment sequences, the hemoglobin endpoint, and limited adverse-event counts. These features describe the study’s question and structure; they do not, by themselves, provide evidence about the size of a treatment effect.

The primary outcome is not analyzable in the posted results. Only three subjects completed the study, and the registry explicitly says the number was too low to analyze the hemoglobin outcome. There is no reported hemoglobin estimate, confidence interval, or statistical test. The result therefore does not show that PEG-Intron changed hemoglobin by a particular amount, nor does it establish that there was no change or no difference from standard care.

The safety counts are also limited. They indicate the number listed as affected in each treatment group, but the registry record does not include the detail needed to judge precision or to make a robust comparative claim. The crossover design and missing information about event timing and assignment further limit interpretation. The listed serious adverse-event term does not provide a full accounting of all events or their clinical context.

These limitations do not mean that the study question was unimportant or that the treatments were equivalent. They mean that the record does not contain enough analyzed outcome information to answer the primary statistical question. General principles about randomization and crossover designs explain what the study structure could support if suitable data and an appropriate analysis were available; they cannot substitute for unreported results.

The appropriate interpretation is bounded by what is recorded: the study enrolled 10 participants, only three completed it, and the hemoglobin outcome was not analyzed because the numbers were too low. The reason for termination, reasons for noncompletion, and details of the intended analysis are not reported in the registry record. Any stronger conclusion about efficacy, equivalence, or comparative safety would go beyond the posted information.

13. Why This Trial Matters Statistically

This study illustrates the distinction between a planned design and an interpretable analysis. Randomization and a crossover structure can support informative comparisons in general, but they cannot guarantee that enough outcome data will be available. The registry record describes a primary hemoglobin endpoint and two treatment sequences, yet it also reports that only three participants completed the study and that the endpoint could not be analyzed.

For biostatisticians and clinical researchers, the central lesson is that enrollment alone does not describe the information available for an endpoint. Completion and measurement at the relevant time points determine what can be estimated. Here, the record does not give the number with baseline and one-year values or explain the pattern of noncompletion, so the amount and representativeness of the usable data cannot be assessed.

The crossover design highlights another practical issue: comparisons can require careful accounting for treatment order and time period. In general, repeated observations from the same participant are not independent, and treatment effects may need to be separated from period or sequence effects. The registry record does not report an analysis addressing these features. That makes the study a useful example of why a design label is not a substitute for a reported statistical model and analysis population.

The adverse-event counts also show why descriptive reporting should be distinguished from inferential comparison. Counts without event timing, uncertainty estimates, and exposure details can inform readers about what was recorded, but cannot establish a precise comparative safety estimate. The primary outcome’s missing analysis and the limited safety detail together make careful wording essential: distinguish unreported results from findings of no effect.

The record matters statistically because it makes visible a common boundary of clinical evidence: a well-defined question can remain unanswered when completion and outcome information are insufficient. Transparent reporting of this distinction prevents absence of an estimate from being mistaken for evidence of no difference.

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 most consequential limitation is that the primary hemoglobin outcome was not analyzed. The registry record attributes this to only three subjects completing the study and says the number was too low for analysis. No numerical outcome data or estimate is reported, so there is no basis in the record for assessing effect size or precision.

Reasons for noncompletion are not reported in the registry record. Without them, readers cannot assess whether missing follow-up might be related to treatment, participant characteristics, or other circumstances. The record also does not give the number of participants with measurements at each endpoint time, the handling of partial data, or the analysis population.

The registry identifies a randomized, unmasked crossover design and describes the treatment sequences, but it does not report how the primary analysis would account for sequence, period, or carryover. It does not report allocation details, a statistical analysis plan, or a sample-size justification. These missing design and analysis details prevent evaluation of whether the intended analysis matched the crossover structure.

The safety information is limited to group-level affected counts and a listed serious adverse-event term. Event-level details, timing, uncertainty estimates, and an explanation of how adverse events were assigned in the crossover periods are not reported. Death counts are also not reported in the registry record.

The status is terminated, but the reason for termination is not reported. The record provides start and primary-completion dates but does not explain the course of recruitment or follow-up. These gaps limit interpretation of both the primary outcome and the safety information; they should not be filled by assumptions about the conduct or reasons for stopping the study.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Phase 2 Study of PEG-Intron in Hereditary Hemorrhagic Telangiectasia — NCT00588146.
• Registry record last updated 2013-02-22; status last verified 2013-02.
• Results first posted 2013-01-28.
• 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

NCT00588146 is a Phase 2 randomized, unmasked crossover study sponsored by Mayo Clinic. It enrolled 10 participants and is listed as terminated. The study start is recorded as 2007-01, and primary completion as 2011-09. The reason for termination is not reported in the registry record.

The planned sequences were PEG-Intron for 6 months followed by standard care for 6 months, or standard care for 6 months followed by weekly subcutaneous PEG-Intron at 1 microgram/kg/week for 6 months. The primary outcome was change in hemoglobin from baseline to one year. The registry record states that only three subjects completed the study, leaving too few for analysis of that outcome.

The record lists serious adverse events affecting 3 of 10 at risk in the PEG-Intron group and 0 of 10 in standard care; other adverse events affected 2 of 10 in each group. Neutropenia is the top listed serious adverse-event term at 30.0%. These counts are descriptive, and the record does not report a comparative statistical analysis of the primary endpoint.