Pegylated Interferon Alfa-2a Maintenance Therapy and Liver Disease Progression in People Infected With Both HIV and Hepatitis C Virus (HCV): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Pegylated Interferon Alfa-2a Maintenance Therapy and Liver Disease Progression in People Infected With Both HIV and Hepatitis C Virus (HCV) (NCT00078403), a randomized phase 2 study. The primary outcome is Time-scaled Change in Metavir Liver Fibrosis Score (SCMFS).

2. Clinical Question

3. Trial Design

SLAM-C was a Phase 2, randomized, open-label, parallel-group study of people infected with both HIV and HCV. The registry reports enrollment of 333 and a completed status. The recorded start is 2004-07, and primary completion is recorded as 2007-05. The sponsor was the National Institute of Allergy and Infectious Diseases (NIAID).

The study had an initial treatment period with pegylated interferon alfa-2a and ribavirin, followed by pathways based on HCV RNA and response at week 12. Participants with detectable HCV RNA and less than a 2 log10 decrease from baseline were randomized for Step 2 to continued PEG-IFN or observation. The continued-treatment arm description lists PEG-IFN 180 mcg weekly; the observation arm description specifies 72 weeks without treatment. Participants meeting the stated response criteria entered a separate pathway in which the arm description says they continued the initial PEG-IFN and ribavirin treatment.

The primary outcome comparison is between the continued-PEG-IFN and observation groups, not the third pathway. The primary outcome data list 33 participants in the PEG-IFN arm and 29 in the observation arm, with no primary outcome value for the third arm. The registry does not report masking beyond identifying the study as open label, nor does it report the detailed sequence-generation or allocation-concealment procedures.

Because assignment followed an initial treatment period and response assessment, the primary comparison addresses outcomes among participants entering the randomized Step 2 pathways. It should not be read as a comparison of starting PEG-IFN versus never receiving treatment. The registry record does not report further protocol details that would explain the precise timing of all assessments or the handling of treatment adherence.

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: 330 participants were to receive 12 weeks of PEG+RBV to determine EVR status. Of the 330, 33 discontinued prior to week 12; 113 were non-EVRs, 80 of whom were randomized between Arms A and B; and 184 achieved EVR, 170 of whom were eligible to continue. 169 of the 170 were assigned to Arm C and one was inadvertently randomized between Arms A and B.

Overall Study

Analysis population for the primary outcome, as defined in the registry: 62 Arm A and B participants who had follow-up liver biopsy performed or those who had Week 72 potential as of May 2, 2007 but no follow-up liver biopsy. In the unadjusted ITT analysis, the participants without SCMFS available were assigned the highest SCMFS (+2).

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.

Population: All Arm A, B and C participants.

6. Primary Endpoint

The registry lists the primary outcome as Time-scaled Change in Metavir Liver Fibrosis Score (SCMFS), measured over Baseline and at week 72 or premature discontinuation.

The primary endpoint was the time-scaled change in Metavir liver fibrosis score, expressed as Metavir units per one year (52 weeks). It was calculated as the difference between the Metavir fibrosis scores from the study exit and study entry liver biopsies, scaled to one year. The registry describes a scale from -4.0 Metavir units per year, indicating reduced fibrosis over time and a positive study outcome, to +4.0 Metavir units per year, indicating increased fibrosis over time.

A liver biopsy provides the tissue assessment used for the Metavir fibrosis score. Expressing the change on an annualized scale makes the reported change interpretable over a common time scale, while retaining the score as a continuous measure. The endpoint therefore concerns change in fibrosis score, rather than a simple count of participants who did or did not cross a specified threshold.

The registry reports the median and inter-quartile range for each arm. The median was 0 in both the PEG-IFN and observation arms. The inter-quartile range was 0 to 1.37 in the PEG-IFN arm and 0 to 2.0 in the observation arm. The outcome timeframe is baseline and week 72 or premature discontinuation. This endpoint was chosen to assess liver fibrosis change; the registry record does not report a justification for selecting it over other possible liver outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous, time-scaled change in Metavir fibrosis score, and the registry reports its median and inter-quartile range. A median is the central value when outcomes are ordered. The inter-quartile range describes the central portion of the distribution, from its lower to its upper quartile. These summaries are useful when a distribution may be skewed or may contain values that make a mean less representative of a typical observation. They do not, by themselves, describe every feature of the distribution.

Why use a rank-based test?

The sponsor reports an exact Wilcoxon rank sum test for the PEG-IFN and observation groups. In general, a rank sum test orders the observed outcomes and compares their ranks across groups. It does not require the comparison to be expressed as a difference between means. The test can be useful for continuous outcomes when a normal-distribution model for the raw values is not appropriate or is not the chosen analysis. The registry record does not report the rationale for choosing this test, so it is not possible to say which distributional concern or analysis-plan decision motivated it.

An exact test evaluates the possible rank arrangements under its null model rather than relying on a large-sample approximation. The posted p-value is 0.58. In general, a p-value describes how compatible the observed test statistic is with the test’s null model; it is not the probability that the null hypothesis is true. Nor does it measure the clinical importance of a difference. The registry record does not report a confidence interval for the primary comparison or a direct rank-based effect estimate.

How should the medians and ranges be read?

Both reported medians are 0, while the inter-quartile ranges differ: 0 to 1.37 for continued PEG-IFN and 0 to 2.0 for observation. A shared median means the center of each group’s ranked outcomes is the same at the reported precision. It does not imply that all observations were equal or that the distributions were the same. The inter-quartile ranges describe variation within each group but are not confidence intervals for the between-group effect. A confidence interval, in general, gives a range of values compatible with the data and the specified method, and conveys uncertainty about an estimated effect. No such interval is reported for this comparison.

What is the role of the missing-outcome rule?

The registry describes an unadjusted ITT analysis in which participants without SCMFS available were assigned the highest SCMFS (+2). In general, an intention-to-treat approach seeks to preserve randomized group assignment in the analysis, while missing-data rules determine how participants without an observed endpoint contribute. Assigning a value is an assumption about the missing outcomes, not a recovery of the unobserved biopsy result. The record does not report the number of missing outcomes, reasons for missingness, or sensitivity analyses using other assumptions. As a result, the robustness of the reported test to alternative missing-data handling cannot be assessed from the registry record.

The endpoint description says the primary population included participants who had follow-up biopsy or had Week 72 potential as of May 2, 2007 without a follow-up biopsy. The meaning of this eligibility wording is not expanded in the registry record. It also does not report a detailed analysis plan explaining how premature discontinuation, biopsy timing, or other deviations were handled beyond the stated missing-value assignment.

What can be inferred from this test?

The test result is evidence about the rank distributions under the specified comparison and analysis. It is not an estimate of how many Metavir units one treatment changed fibrosis relative to the other, and it does not establish equivalence or non-inferiority. General interpretation of a non-significant result must account for both the estimated effect and its uncertainty; here, the registry does not post a confidence interval or an effect estimate suitable for that assessment. The posted summaries and p-value should therefore be read together, without treating the p-value as a measure of effect size.

The record lists 18 outcome measures and 17 posted secondary outcomes. General statistical practice recognizes that testing multiple outcomes can increase the chance of obtaining one or more small p-values by chance if no adjustment or prespecified testing strategy is used. The registry record does not report whether multiplicity was controlled, how primary and secondary tests were ordered, or whether any interim analyses were conducted. No conclusions about those design choices can be drawn from the posted information.

10. Analyses Reported by the Sponsor

The registry reports the sponsor’s primary comparison as an exact Wilcoxon rank sum test, with p = 0.58. It also reports a median of 0 in each group and inter-quartile ranges of 0 to 1.37 for continued PEG-IFN and 0 to 2.0 for observation. These are the sponsor’s posted summaries and inferential result.

No recalculated between-group estimate or test result is available for this median endpoint in the posted results. The available summary statistics do not supply the participant-level ranks needed to reproduce the exact Wilcoxon test. Accordingly, there is no independent recalculation to compare with the sponsor’s analysis, and no discrepancy is indicated. The sponsor’s result remains the relevant reported inferential analysis.

The sponsor’s test should still be interpreted within its limits. The record does not post a confidence interval for the comparison, the participant-level outcome data, or sensitivity analyses for the missing-outcome assignment. Thus the reported p-value does not establish the size or precision of a treatment effect. It describes the sponsor’s rank-based test for the defined primary comparison and analysis population.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 18 outcome measures and 17 posted secondary outcomes. The primary endpoint is the time-scaled change in Metavir liver fibrosis score. Secondary outcomes include detectable HCV viral load, change in liver inflammation score, anemia, neutropenia, thrombocytopenia, depression or other psychological events, high-grade signs or symptoms or laboratory values, and dose modifications, temporary stops, or premature treatment discontinuations. The record does not report a multiplicity adjustment, a testing hierarchy, or whether these outcomes were treated as confirmatory or exploratory.

In general, when many outcomes are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses multiple testing. This does not mean that any particular result is false; it means that interpretation depends on knowing which outcomes were prespecified and how the family of tests was handled. Those details are not reported in the registry record. The number of analyses listed for the primary outcome is 1, but this alone does not describe the broader testing strategy across outcomes.

The primary outcome description includes 62 participants in the PEG-IFN and observation groups who had follow-up biopsy or Week 72 potential as of May 2, 2007 without follow-up biopsy. It states that, in the unadjusted ITT analysis, participants without SCMFS available were assigned the highest SCMFS (+2). The record does not state how many participants were assigned this value, why their scores were unavailable, or whether results were examined under other missing-data assumptions. It also does not report a separate complete-case result.

These omissions limit assessment of how sensitive the primary comparison is to missing outcomes and how the secondary findings should be interpreted alongside the primary test. The registry record does not report an interim-analysis plan, a sample-size justification, or further details of the statistical analysis plan. The sample-size illustrations associated with the observed effect are planning exercises, not observed power and not evidence of the trial’s original design rationale.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: neutropenia (7.7%), basedow's disease (2.4%), neutrophil count (2.4%), neutrophil count decreased (2.4%), anaemia (2.3%).

The serious adverse event summaries list 6 affected participants among 44 at risk in the continued-PEG-IFN group, 2 among 42 in the observation group, and 37 among 169 in the PEG-IFN and ribavirin continuation group. The record also lists other adverse events affecting 43 among 44, 41 among 42, and 166 among 169, respectively. These are group-level counts as posted; they should not be treated as a direct comparison of risk without accounting for the study’s treatment pathways, follow-up, and safety definitions.

The most frequently listed serious terms include neutropenia at 7.7%, Basedow's disease at 2.4%, neutrophil count at 2.4%, neutrophil count decreased at 2.4%, anaemia at 2.3%, and lymphoma at 2.3%. These term-specific percentages are not the same as the proportions with any serious adverse event. The registry record does not report death counts. It also does not provide enough detail in these summaries to assess event timing, duration, severity grading beyond the serious classification, or attribution to treatment.

Safety counts describe reported events in the registry record; they do not establish that an event was caused by an intervention. The third arm’s safety counts are included even though that arm has no posted primary endpoint value in the reported comparison.

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

The result answers a narrow statistical question: in the reported primary comparison, how did the annualized Metavir fibrosis score distributions differ between participants assigned to continued PEG-IFN and those assigned to observation after an initial PEG-IFN and ribavirin period? The posted medians were both 0, and the sponsor’s exact Wilcoxon rank sum test yielded p = 0.58. These results describe the trial’s reported analysis; they do not establish that the treatment strategies have identical effects.

The result does not show that no participant’s fibrosis score changed. The inter-quartile ranges extend above 0 in both groups, and the primary analysis assigned +2 to participants without SCMFS available in the unadjusted ITT analysis. The registry does not report a confidence interval for a between-group effect, so it does not provide a posted range for the magnitude of differences compatible with the data.

The finding also does not establish equivalence or non-inferiority. Such conclusions require a prespecified margin and an analysis designed to assess that margin; neither is reported in the registry record. A p-value that does not indicate strong evidence against a null model is not proof of no difference, and it does not measure the probability that a treatment works.

The primary comparison is limited to the randomized PEG-IFN and observation pathways following the initial treatment period and response assessment. It is not a comparison of starting treatment versus no prior treatment, and it does not provide a primary outcome result for the third arm. Its relevance to other groups or treatment settings cannot be established from this registry result alone.

The record also leaves uncertainty about missing outcomes, multiplicity, and precision. It does not report the number of participants whose endpoint values were assigned, sensitivity analyses, or a confidence interval. Therefore, the most defensible reading is descriptive: the posted group medians were the same at the reported precision, the central ranges were as stated, and the sponsor’s rank-based test reported p = 0.58. Broader conclusions go beyond these posted results.

14. Why This Trial Matters Statistically

This trial illustrates why a clinical outcome should be interpreted through its measurement and analysis, not through a p-value alone. The primary endpoint is a biopsy-based fibrosis score change scaled to one year. Its median and inter-quartile range describe different features of the outcome distribution, while the exact Wilcoxon rank sum test compares ranked outcomes across the two randomized groups. These summaries answer related but distinct questions.

The result also highlights the importance of identifying the actual randomized population. Participants first received PEG-IFN and ribavirin, and later pathways depended on HCV RNA and response. The primary comparison therefore concerns continued PEG-IFN versus observation within the defined randomized pathway; it is not a general comparison of treatment initiation against no treatment.

Missing outcome handling is another central statistical issue. The registry states that participants without SCMFS available were assigned +2 in the unadjusted ITT analysis. That rule affects what the reported analysis represents, yet the number of assigned values and sensitivity analyses are not reported. Readers cannot assess robustness to other assumptions from the posted record.

Finally, the record reports a p-value but not a confidence interval or a between-group effect estimate. The equal medians do not prove equivalence, and the p-value does not quantify effect size. The study is therefore a useful example of the need to distinguish descriptive summaries, hypothesis tests, precision, and claims about clinical meaning. The planning illustrations based on the observed effect are not observed power and should not be mistaken for the trial’s original design justification.

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 registry record gives limited detail about the statistical plan. It does not report the rationale for the primary test, a confidence interval for the comparison, a direct treatment-effect estimate, the original sample-size justification, or whether interim analyses were planned or conducted. These omissions limit independent evaluation of the analysis choices and precision.

The endpoint depends on entry and exit liver biopsies, while the primary population description also includes participants with Week 72 potential but no follow-up biopsy. The record states that missing SCMFS values were assigned +2 in the unadjusted ITT analysis, but it does not report the number of such assignments, reasons for missingness, or sensitivity analyses. The impact of this rule on the result therefore cannot be assessed from the registry record.

The primary outcome data cover the PEG-IFN and observation groups; no primary outcome value is posted for the third arm. The arm descriptions are abbreviated in the registry record, limiting detail about the treatment regimen and pathway beyond the stated assignment descriptions. The open-label design is recorded, but the record does not describe procedures to limit assessment bias for the biopsy outcome.

The registry lists multiple outcomes but does not report whether multiplicity was addressed or how secondary analyses were intended to inform conclusions. Safety summaries provide affected counts and selected serious-event terms, but the record does not report death counts, event timing, or treatment attribution. Finally, this primary comparison follows an initial treatment period and response-based pathway, so it does not directly address populations or treatment decisions outside that trial context.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Pegylated Interferon Alfa-2a Maintenance Therapy and Liver Disease Progression in People Infected With Both HIV and Hepatitis C Virus (HCV) — NCT00078403.
• Registry record last updated 2021-11-08; status last verified 2016-11.
• Results first posted 2011-04-27.
• 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

SLAM-C (NCT00078403) was a completed, Phase 2, randomized, open-label, parallel-group study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). It enrolled 333 people infected with both HIV and HCV. The recorded study start is 2004-07 and primary completion is 2007-05.

The primary outcome was time-scaled change in Metavir liver fibrosis score, expressed as Metavir units per one year (52 weeks). In the reported PEG-IFN and observation groups, the median was 0 in both arms; inter-quartile ranges were 0 to 1.37 and 0 to 2.0, respectively. The sponsor reported an exact Wilcoxon rank sum test with p = 0.58. Participants without SCMFS available were assigned +2 in the unadjusted ITT analysis. The registry does not report a confidence interval for the comparison.