SCH 54031 PEG12000 Interferon Alfa-2b (PEG Intron, MK-4031) vs. INTRON®A (SCH 30500, MK-2958) as Adjuvant Therapy for Melanoma (C98-135, MK-4031-002): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for SCH 54031 PEG12000 Interferon Alfa-2b (PEG Intron, MK-4031) vs. INTRON®A (SCH 30500, MK-2958) as Adjuvant Therapy for Melanoma (C98-135, MK-4031-002) (NCT03552549), a randomized phase 2, phase 3 study. The primary outcome is Progression-free Survival (PFS).

2. Clinical Question

3. Trial Design

This was a randomized, controlled, multicenter, open-label Phase II/III study with a parallel-group design. Participants were assigned to PEG-Intron or INTRON A as adjuvant therapy after surgery for Stage III node-positive cutaneous melanoma. The registry record reports enrollment of 126. It lists 63 participants at risk for serious adverse events in each treatment group. The record does not provide further details about the randomization procedure, allocation concealment, or the number of participating centers.

Masking was listed as none. Participants and study personnel therefore were not described as blinded to treatment assignment. This matters when interpreting outcomes that involve clinical judgment or reporting, although the primary outcome was intended to include confirmation by Independent Central Review. The record says that this confirmation was not collected because the study ended early.

The treatment strategies differed. PEG-Intron was given subcutaneously once weekly for 2 years post-surgery. INTRON A began with an intravenous schedule for 4 weeks, followed by subcutaneous dosing three times per week for 48 weeks. Those protocol descriptions establish the intended regimens, but the registry record does not say how much treatment participants actually received, whether they completed treatment, or whether schedules changed during the study.

The study began on 1998-08-05, and primary completion was recorded as 2001-02-19. Its status is terminated. The reason for termination and any resulting changes to the planned analyses are not reported in the registry record, apart from the statement that central confirmation of PFS was not collected and the planned PFS analysis therefore could not be performed.

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: All randomized participants. Due to the early termination of this study, confirmation of PFS by Independent Central Review was not collected and; therefore, PFS could not be analyzed as planned per protocol.

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 Progression-free Survival (PFS), measured over From time of randomization to time of progression or death (up to approximately 26 months).

The primary endpoint, progression-free survival (PFS), measures the time from randomization until disease progression or death from any cause. In this study, progression was to be assessed by clinical observation, with recurrence documented using appropriate radiographic and histologic methods. The record says recurrence was to be confirmed by Independent Central Review.

General: A time-to-event endpoint uses both whether an event occurs and how long it takes to occur. It can represent the course of disease over follow-up more fully than a simple count of participants with an event at a fixed visit. Its interpretation depends on a clear event definition, adequate follow-up, and consistent assessment. In an open-label study, independent review can help standardize outcome assessment, but the registry record says that the planned central confirmation was not collected.

The timeframe is described as from randomization to progression or death, up to approximately 26 months. Because the study ended early, the record states that PFS could not be analyzed as planned per protocol. It does not report a PFS estimate, event count, confidence interval, or comparative test result. Thus, the endpoint definition is available, but a treatment comparison for this primary outcome is not.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General: randomized comparison. Random assignment is intended to make treatment groups comparable, on average, with respect to factors that could influence outcomes. A controlled parallel-group design compares participants assigned to different treatment strategies during the same study. Randomization does not guarantee identical groups, especially in a finite trial, and it does not remove the need to describe the analysis population and follow-up. The registry record identifies the study as randomized and parallel-group but does not report the randomization procedure, allocation concealment, or detailed analysis methods.

General: open-label assessment. In an open-label study, treatment assignment is not masked. Knowledge of assignment can affect decisions, reporting, or the timing of assessments, particularly for outcomes requiring clinical judgment. A prespecified, independent review can provide a more consistent assessment of events across groups. Here, the record says PFS recurrence was to be confirmed by Independent Central Review, but also says that this confirmation was not collected after early termination. The registry record does not describe an alternative adjudication process or a sensitivity analysis addressing this issue.

General: time-to-event analysis. PFS is a time-to-event outcome: the event is progression or death, and the measured time starts at randomization. In a complete analysis, participants who have not had an event by the end of observed follow-up may contribute information up to their last known event-free assessment. Such observations are commonly treated as censored, rather than as proof that an event will never occur. The registry record does not report the censoring rules, follow-up distribution, event counts, or methods used to estimate or compare PFS. Since the planned PFS analysis was not performed as specified, no method-specific PFS estimate is available to interpret.

General: estimates and uncertainty. A treatment-effect estimate would describe the observed contrast between groups for a defined outcome. A confidence interval describes the range of values reasonably compatible with the data and analysis assumptions; a wider interval indicates less precision. A P-value, when used, assesses how compatible the observed data are with a specified null hypothesis under the model. These measures answer different questions and are not substitutes for the endpoint definition, design, or completeness of follow-up. The registry record does not report a PFS effect estimate, confidence interval, or P-value.

General: event counts and exposure. Simple counts of participants with adverse events can describe what was recorded, but they may not capture differences in duration of exposure or time under observation. Comparisons can also depend on how events were defined, collected, and attributed. The record lists participants at risk and affected for serious and other adverse events, plus deaths. It does not report exposure-adjusted rates, event-onset timing, attribution, or a formal comparative safety model. Those absent details limit interpretation of the counts.

General: planning illustrations. A sample-size calculation asks how much information a planned study might need to detect a specified effect under stated assumptions. It is a planning exercise, not an observed result, and it is not a measure of the probability that a completed trial's finding is correct. The registry record describes planning illustrations using a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event outcomes, the stated calculation basis is total events using the Schoenfeld method; other calculations are expressed as participants per arm. These are planning assumptions, not evidence that the trial was designed or powered using those assumptions. The registry record does not report a sample-size justification or the trial's original design assumptions.

General: early termination and analysis. Early termination can reduce the amount of follow-up and outcome information available, and can prevent a planned analysis from being completed. It does not establish the direction or size of a treatment effect. In this study, the record specifically links early termination to the absence of Independent Central Review confirmation and states that PFS could not be analyzed as planned per protocol. It does not report whether an interim analysis occurred, why termination happened, or whether any alternative analysis was performed. Those details should not be inferred from the study status alone.

General: populations for analysis. An analysis population specifies which randomized participants or treated participants contribute to an estimate. An all-randomized population generally preserves the randomized comparison, while a population based on treatment received or protocol adherence answers a different question and may be more susceptible to selection. The primary outcome description names all randomized participants as its population. However, because the planned PFS analysis was not completed, the record does not provide an analyzed participant count or explain handling of withdrawals, missing assessments, or protocol deviations.

10. Multiplicity, Missing Data and Analysis Populations

The registry record identifies PFS as the primary outcome and Overall Survival as a secondary outcome. It describes the primary endpoint definition and intended timeframe, but says PFS could not be analyzed as planned because the study terminated early and Independent Central Review confirmation was not collected. No comparative result for Overall Survival is reported in the registry record.

When a study evaluates multiple outcomes, time points, or treatment comparisons, the chance of a false-positive finding can increase if the analyses are treated as independent opportunities to claim a difference. Statistical plans may address this through a prespecified hierarchy, adjusted significance thresholds, or other procedures. The registry record does not report a multiplicity strategy, testing hierarchy, or adjustment across outcomes.

The record also does not report whether interim analyses were planned or conducted, how missing outcome assessments were handled, or what rules were used for censoring PFS observations. It names all randomized participants as the primary outcome population, but does not provide the number included in a completed PFS analysis or explain deviations from that population. These omissions matter because the analysis population, follow-up, missingness, and decision rules can affect an estimate and its uncertainty.

The available information therefore does not establish how multiplicity, missing data, or analysis-population decisions were handled in a completed efficacy analysis. These statistical-plan details are not reported in the registry record. The absence of a reported method should not be mistaken for evidence that no such method existed outside 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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hepatic enzyme increased (6.3%), lymphadenopathy (4.8%), vertigo (3.2%), nausea (3.2%), vomiting (3.2%).

The registry record lists serious adverse events affecting 24 of 63 participants in the PEG-Intron group and 19 of 63 in the INTRON A group. Other adverse events affected 61 of 63 and 60 of 63, respectively. Deaths were recorded for 11 participants in the PEG-Intron group and 9 in the INTRON A group. These are descriptive counts, not adjusted comparisons.

The listed serious-event terms and percentages are hepatic enzyme increased, 6.3%; lymphadenopathy, 4.8%; vertigo, 3.2%; nausea, 3.2%; vomiting, 3.2%; and injection site necrosis, 3.2%. The record does not give treatment-specific counts for each listed term in the information, so those percentages should not be assigned to one arm or interpreted as a comparison between arms.

General: A count of participants affected is not necessarily a count of all event episodes. Counts also do not show when events occurred, how long participants were exposed, whether events were considered treatment-related, or how severe they were beyond the serious-event classification. The registry record does not report those details or a statistical comparison of safety between regimens. Recorded deaths are not, by themselves, evidence that treatment caused the deaths.

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

The most defensible conclusion is about the limits of the available evidence. This randomized study was intended to compare two adjuvant interferon regimens using PFS as its primary outcome. The registry record says the study was terminated early and that the planned independent confirmation of PFS was not collected. Consequently, the planned PFS analysis could not be completed as specified.

This does not show that the regimens had the same PFS, and it does not show that either regimen had better PFS. No comparative PFS estimate or measure of its precision is reported. The study's design establishes the question it was meant to address; it does not supply the missing outcome comparison.

The safety counts and serious-event terms describe what the registry record lists, but they do not establish causation or a reliable relative safety effect. Interpreting them would require further information about event definitions, exposure, follow-up, attribution, and analysis. The record does not provide those details. Overall Survival is identified as a secondary outcome, but its result is not reported.

General: Statistical evidence is most informative when the study's outcome is defined in advance, assessed consistently, analyzed using a specified method, and reported with an estimate and its uncertainty. When a planned outcome analysis is unavailable, the correct interpretation is uncertainty about that comparison, not a finding of no effect. The registry record supports understanding the trial's intent and selected descriptive safety data, but not a quantified efficacy conclusion.

13. Why This Trial Matters Statistically

This trial illustrates the difference between a randomized design and an interpretable randomized result. Randomization is a strength of the design because it aims to balance groups at assignment. But a planned comparison still depends on collecting and analyzing the primary outcome. The registry record says that early termination prevented the intended central confirmation of PFS, leaving the primary comparison unavailable as planned.

It also highlights the role of endpoint ascertainment. PFS depends on defining progression and determining when it occurs. The protocol description called for clinical observation, appropriate radiographic and histologic documentation, and Independent Central Review. The record's statement that central confirmation was not collected is therefore directly relevant to the endpoint, not merely a reporting detail.

The trial also shows why descriptive safety counts should be kept separate from comparative conclusions. Counts can tell readers how many participants were listed as affected, but do not replace a specified analysis that accounts for exposure, follow-up, and uncertainty. The record provides some safety figures while leaving important interpretive details unreported.

Finally, planning assumptions should not be confused with the trial's own design rationale or with observed evidence. A sample-size illustration based on an observed effect is a planning calculation; it cannot restore an unperformed primary analysis or establish the precision of a missing comparison. The record does not report the original sample-size justification. Taken together, these features make the trial a useful example of how design, outcome collection, analysis completion, and reporting all contribute to the strength of statistical conclusions.

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 limitation for interpreting efficacy is explicit: the study terminated early, Independent Central Review confirmation of PFS was not collected, and PFS could not be analyzed as planned per protocol. The registry record reports no PFS treatment-effect estimate, confidence interval, P-value, or group-specific event data. It also does not report a result for the secondary outcome Overall Survival.

The reason for termination is not reported in the registry record. The record does not state whether interim analyses occurred, whether the protocol or analysis plan changed, or whether any alternative PFS analysis was attempted. It does not report the number of participants with usable follow-up, event timing, censoring rules, missing-assessment handling, or the actual analysis population for PFS.

The open-label design is another consideration, especially for outcome assessment and adverse-event reporting. The planned independent review could have helped standardize progression assessment, but was not collected. The record does not describe a substitute review process or provide sensitivity analyses. It also does not report detailed baseline characteristics, actual treatment exposure, adherence, treatment discontinuation, or changes to the stated regimens.

For safety, the record offers counts of affected participants and deaths, along with several serious-event terms and percentages, but does not report event attribution, timing, exposure-adjusted rates, or uncertainty for between-group comparisons. The record also does not provide a detailed statistical analysis plan, multiplicity procedures, or the original sample-size justification. These gaps restrict interpretation to the design description and the specific descriptive data recorded.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: SCH 54031 PEG12000 Interferon Alfa-2b (PEG Intron, MK-4031) vs. INTRON®A (SCH 30500, MK-2958) as Adjuvant Therapy for Melanoma (C98-135, MK-4031-002) — NCT03552549.
• Registry record last updated 2019-07-24; status last verified 2019-07.
• Results first posted 2019-07-24.
• 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

NCT03552549 was a randomized, controlled, multicenter, open-label Phase II/III parallel-group study of PEG-Intron versus INTRON A as adjuvant therapy for resected Stage III node-positive cutaneous melanoma. Enrollment was 126. The study began on 1998-08-05, primary completion was 2001-02-19, and the status is terminated.

The primary endpoint was PFS, defined as time from randomization to progression or death from any cause. The registry record states that early termination meant Independent Central Review confirmation was not collected, so PFS could not be analyzed as planned per protocol. Overall Survival is listed as a secondary outcome, without a reported result. The record includes descriptive serious and other adverse-event counts and recorded deaths, but no comparative efficacy estimate or detailed comparative safety analysis.