A Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF) (NCT02871401), a randomized phase 1 study. The primary outcome is Proportion of Subjects Who Discontinue Study Drug Due to Adverse Events.

2. Clinical Question

This is a safety and tolerability question, not a test of whether either regimen changes the course of IPF. The study description identifies adverse-event type, frequency, and duration as the basis for assessing safety and tolerability. Its stated primary endpoint narrows that broader topic to discontinuation attributed to adverse events. A participant who has an adverse event but continues study drug would not meet this particular endpoint on that basis, although the event may be represented in other safety outcomes. The registry record also names secondary outcomes related to adverse-event counts and serious adverse events. Those measures describe different aspects of safety and should not be treated as interchangeable with discontinuation.

3. Trial Design

The registry identifies NCT02871401 as a completed Phase One-B pilot trial of herpesvirus treatment in IPF. It was randomized, used a parallel-group model, and was listed as quadruple masked. The study description calls it a single-center, prospective, randomized, placebo-controlled, double-blind pilot study. The registry’s masking field and the study-description wording are not identical; the record does not explain that difference. Vanderbilt University Medical Center is listed as sponsor.

The registry lists enrollment of 31. The study description says 30 subjects would be enrolled and randomized, with 20 assigned to pirfenidone plus valganciclovir and 10 to pirfenidone plus placebo. The posted primary-outcome groups instead contain 20 participants in the valganciclovir group and 11 in the placebo group. These are different record entries, and the reason for the difference is not reported in the registry record. The outcome comparison should therefore be read using the group counts attached to that posted result.

The stated treatment period was 12 weeks. The description says participants would be offered bronchoscopy with bronchoalveolar lavage at study initiation and after treatment, and would then be followed at routine clinic visits at 6, 9, and 12 months for data collection. The primary endpoint itself is specified at 12 weeks, so it does not summarize all later follow-up. The registry lists a start date of 2018-01-03, a primary completion date of 2020-01-31, and a completed status. Details such as the randomization procedure, allocation concealment, and the rationale for the planned group sizes 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

Reasons for not completing this period:

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 Proportion of Subjects Who Discontinue Study Drug Due to Adverse Events, measured over 12 weeks.

The primary endpoint is the number of participants who discontinued study drug because of adverse events during the 12-week treatment period. The registry describes the measure as a proportion of study subjects, but the posted result is expressed as participant counts in each group. One participant in the valganciclovir group and none in the placebo group were recorded for this outcome. The group sizes for this result are 20 and 11, respectively.

Discontinuation is a clinically interpretable safety outcome because it captures adverse events serious or troublesome enough, or otherwise judged consequential enough, to lead to stopping assigned study drug. It is not a complete measure of all adverse events: events that do not lead to stopping treatment are outside the endpoint definition. Nor does it describe severity, duration, or the full range of event types. Those broader aspects are addressed in the study description and in separately named safety outcomes.

As a pilot endpoint, this measure can describe what happened in the trial groups, but the small number of recorded discontinuations limits precision. The result should be read as a comparison of observed event counts over a specified treatment period, not as a definitive estimate of safety in a broader population.

7. Results Posted in the Registry

• Valganciclovir: 5.0% (1/20) versus 0.0% (0/11) on control; risk difference 5.0 percentage points (95% CI -4.6 to 14.6); unadjusted two-proportion z-test p = 0.451.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary result is a two-group comparison of a binary outcome: whether a participant discontinued study drug due to adverse events during the 12-week period. A binary outcome has two possible states for each participant, such as event or no event. The registry presents counts for this endpoint, rather than a continuous measurement such as a laboratory value. The corresponding group sizes are 20 for valganciclovir and 11 for placebo.

What does the risk difference represent?

A risk difference compares the event proportion in one group with the event proportion in another group by subtraction. It is expressed on the proportion scale, where zero corresponds to equal observed proportions. A positive value for the reported direction means the event proportion is higher in the valganciclovir group than in the placebo group; a negative value means it is lower. The registry reports a risk difference of 0.05. This is an absolute contrast, not a relative risk or an odds ratio, and it should not be described as a percentage change in risk.

For a simple illustration of the underlying idea, the event count is considered in relation to the number of participants in each group. The registry’s risk-difference estimate is the reported comparison; no alternative estimate has been calculated for this explanation. The point estimate should be considered with its confidence interval, especially because only one event is recorded across the two groups.

What does the confidence interval add?

In general, a confidence interval describes the uncertainty around an estimate under a statistical procedure and its assumptions. It provides a range of values that are reasonably compatible with the observed data under that procedure. It is not a guarantee that the true value lies in the particular interval, and it does not show the probability that a hypothesis is true. For this result, the interval includes zero and extends to either side. That means the posted data do not precisely distinguish a positive risk difference from no difference or a negative risk difference.

The registry gives the interval bounds to more than three decimal places, while the reporting convention for this analysis limits displayed decimals to three. The important interpretive features are that the interval crosses zero and is wide relative to the point estimate. The exact interval calculation method is not reported in the registry record, so no specific method should be inferred from the bounds alone.

How should the p-value be read?

The posted p-value is unadjusted and is 0.451. In general, a p-value quantifies the extremeness of data under a null hypothesis and a specified statistical model. It does not measure the size or importance of an effect, and it is not the probability that chance alone produced the result. A p-value does not establish equivalence when it is not small. The registry does not report the test used, its assumptions, or whether it was prespecified in a statistical analysis plan.

The estimate, interval, and p-value answer related but different questions. The estimate gives the direction and magnitude of the observed comparison. The interval communicates uncertainty about that estimate. The p-value summarizes compatibility with a null model under a particular test. None should be interpreted in isolation, and together they do not overcome the limited information in a comparison with sparse events.

What is the role of the planning illustrations?

Sample-size illustrations based on an observed effect are planning calculations, not observed trial outcomes. The stated assumptions for those illustrations are a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. Such calculations describe hypothetical future planning under those assumptions. They are not observed power, and they do not demonstrate that the present trial was adequately powered. The trial’s own sample-size justification is not reported in the registry record.

In general, over-dispersion matters when data vary more than a model assumes: standard errors can then be understated, and confidence intervals may be too narrow if the extra variation is ignored. This primary outcome is a participant-level binary count, and no over-dispersion model is reported. That concept should not be mistaken for a method used in this trial. More broadly, the statistical model, interval procedure, test procedure, covariate adjustment, and handling of missing outcomes are not reported in the registry record.

10. Confidence Intervals and Precision

The primary estimate is a risk difference of 0.05, based on one recorded discontinuation in the valganciclovir group and none in the placebo group. The confidence interval crosses zero and extends in both directions. It therefore permits interpretations ranging from a lower event proportion with valganciclovir to a higher event proportion, including no difference. The interval is more informative about uncertainty than the point estimate alone, but it remains broad for this sparse outcome.

In general, a confidence interval is a statistical range constructed to reflect sampling uncertainty under a specified procedure. It is not a range containing every plausible explanation, and its coverage depends on the method and assumptions. The registry record does not report the interval method. The posted bounds have more than three decimal places, which are not reproduced in this explanation; their key feature is that they straddle zero.

Precision is limited by the small group sizes and low event count. In such circumstances, one additional or fewer event can materially change the estimated risk difference. The reported p-value of 0.451 is consistent with the absence of a precise separation from zero under the posted test, but it does not establish that the groups have equal risks. Nor does the confidence interval establish that every value within its range is equally likely. The appropriate conclusion is that the estimate is uncertain, rather than that the comparison demonstrates equivalence or a clear difference.

These data describe the trial’s observed participants and 12-week endpoint. Precision for this particular comparison does not determine precision for serious adverse events, all adverse events, later follow-up, or outcomes in a broader population. Each outcome has its own number of events, definition, and uncertainty.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists five outcome measures and names three secondary outcomes: adverse-event number, serious adverse events, and total adverse events. It reports no analyses. No adjustment for multiple comparisons, hierarchy among outcomes, or strategy for distinguishing confirmatory from exploratory results is reported in the registry record. When several outcomes are examined, the chance of at least one apparently unusual result can increase; in general, multiplicity methods address that issue by changing how evidence is assessed. No such method should be assumed for this trial.

The primary discontinuation endpoint is conceptually different from the secondary safety outcomes. A participant may experience an adverse event without discontinuing treatment, and serious adverse events are classified separately in the registry. These outcomes can overlap in participants, but their definitions and counts should not be combined. The record does not provide a complete outcome-by-outcome analysis plan or identify which secondary comparisons, if any, were inferential.

Missing-data handling is not reported in the registry record. The record does not specify how a participant with an unavailable 12-week status would be classified, whether any primary endpoint values were missing, or whether a sensitivity analysis was conducted. The population used for the primary analysis is also not reported. The record does not specify whether all randomized participants were included, whether analysis followed assignment regardless of treatment received, or whether any participants were excluded from the endpoint analysis.

These omissions affect how fully the result can be audited. They do not imply that data were missing or that participants were excluded; those details are simply not reported in the registry record. Without analysis-population definitions, missing-data procedures, and a prespecified multiplicity strategy, the posted result is best interpreted as the registry’s reported outcome comparison rather than as a complete account of the trial’s statistical plan.

12. 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: prostate cancer (9.1%), rash (5.0%), hospitalization (5.0%).

The registry reports serious adverse events for 2 of 20 participants in the valganciclovir group and 1 of 11 participants in the placebo group. It reports other adverse events for 14 of 20 and 4 of 11 participants, respectively. Deaths are listed as 0 in the valganciclovir group and 1 in the placebo group. These are descriptive group counts; they do not by themselves establish that a treatment caused an event or that an event was unrelated to treatment.

The term “serious adverse event” is not interchangeable with “severe” or with any adverse event that led to discontinuation. The record’s group counts do not provide event timing, individual clinical circumstances, or an adjusted comparison. It also lists prostate cancer at 9.1%, rash at 5.0%, and hospitalization at 5.0% among the top serious-event terms. The record does not clarify in this summary how those terms map to the group-level counts, so they should not be assigned to a group or treated as a complete list of events.

Because the group sizes and event counts are limited, these summaries are imprecise and should be read as descriptions of what was recorded during the trial, not as stable estimates for other settings.

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

The result establishes that the registry recorded one discontinuation due to adverse events in the valganciclovir group and none in the placebo group during the 12-week endpoint period. The reported risk difference is 0.05, and the unadjusted p-value is 0.451. The confidence interval crosses zero, so the data do not precisely establish the direction or size of the difference. These findings are descriptive of the trial record and do not establish that the two groups are equivalent.

The endpoint captures a particular decision-related outcome: stopping study drug because of adverse events. It does not count every adverse event as an endpoint event, characterize the full severity or duration of all events, or summarize every aspect of tolerability. Separate adverse-event and serious-adverse-event counts provide additional safety information, but they also have limitations and should not be collapsed into the primary endpoint.

This was a pilot trial with limited numbers of participants and sparse primary events. The record’s planned allocation in the study description differs from the groups attached to the posted endpoint, and the reason is not reported. The registry does not report an analysis population, missing-data method, or detailed statistical plan. These features limit how confidently the result can be generalized or used to compare risk beyond this trial.

The record does not support conclusions about clinical benefit for IPF, disease progression, or outcomes beyond the posted measures. It also does not support advice about treatment choice. Its contribution is narrower: it documents the trial design and a small set of safety outcomes, while leaving substantial statistical uncertainty around the primary group comparison.

14. Why This Trial Matters Statistically

Pilot trials can be statistically informative even when they cannot provide precise estimates. They can document how a randomized comparison was organized, identify outcomes that were collected, and show the scale of uncertainty associated with sparse events. In this trial, the primary safety endpoint had one recorded event in one group and none in the other. That pattern makes the confidence interval essential: the point estimate alone does not convey how little information the event counts contain about the underlying group difference.

The record also illustrates why trial descriptions and posted outcome data need to be read together. The study description gives a planned enrollment and allocation, while the primary endpoint data show group counts that differ from those plans. The discrepancy is visible, but its explanation is not reported. Clear reporting of participant flow and analysis populations would help readers understand how planned allocation relates to the results.

Statistically, a non-small p-value should not be used as proof of no difference, especially when estimates are imprecise. Likewise, an observed difference should not be treated as a stable estimate merely because it has a numerical direction. Confidence intervals, event counts, endpoint definitions, and missing reporting all contribute to interpretation.

The registry lists other safety outcomes, but no analyses are posted. That distinction matters: the existence of named outcomes does not mean that comparative statistical results are available for them. The trial is therefore useful as a case for careful reading of descriptive safety data, uncertainty, and the limits of what a small pilot comparison can establish.

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 leaves important design and analysis details unspecified. It does not report the randomization sequence method, allocation concealment, detailed eligibility criteria, statistical analysis plan, or the method used for the primary confidence interval and p-value. The masking field says quadruple, whereas the study description uses double-blind wording; the record does not explain the difference. These omissions make it difficult to assess some potential sources of bias or reproduce the inferential analysis.

The stated planned enrollment and allocation differ from the group counts attached to the posted primary outcome. The record lists enrollment of 31, while the study description says 30 would be enrolled, with 20 assigned to valganciclovir and 10 to placebo; the outcome groups are 20 and 11. The reason is not reported in the registry record. Participant flow, treatment adherence, withdrawals for reasons other than the primary endpoint, and the analysis population are not described in the posted result summary.

The primary event count is sparse, limiting precision. The follow-up for the primary endpoint is 12 weeks, so it does not represent all later safety experience. Although the description notes later clinic visits and bronchoscopy offers, results for those procedures and follow-up are not detailed in the registry record for this analysis. The registry names secondary safety outcomes but reports no analyses, limiting comparative interpretation beyond the primary endpoint.

The trial is described as single-center and pilot, which constrains the reach of its findings. No sample-size justification for the trial is reported in the registry record. The planning illustrations based on the observed effect are not a substitute for that justification and are not observed power.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Pilot Trial of Herpesvirus Treatment in Idiopathic Pulmonary Fibrosis (IPF) — NCT02871401.
• Registry record last updated 2022-04-29; status last verified 2022-04.
• Results first posted 2022-04-29.
• 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

NCT02871401 is a completed randomized, parallel-group Phase One-B pilot trial sponsored by Vanderbilt University Medical Center. It compared valganciclovir plus pirfenidone with placebo plus pirfenidone in people with IPF and evidence of current or past EBV or CMV infection. The primary endpoint was discontinuation of study drug due to adverse events during 12 weeks.

The posted primary outcome records one event among 20 participants in the valganciclovir group and none among 11 participants in the placebo group. The reported risk difference is 0.05, with an unadjusted p-value of 0.451; the confidence interval crosses zero. The record also lists serious and other adverse events and deaths. The result is limited by sparse events, imprecision, and statistical and participant-flow details that are not reported in the registry record.