Use of Convalescent Plasma for COVID-19: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Use of Convalescent Plasma for COVID-19 (NCT04408040), a non-randomized phase 2 study. The primary outcome is Arms 1 & 2: Number of COVID-19 Infected Patients in Severe, High Risk & Health Care Provider Cohorts Who Survive the Infection.

2. Clinical Question

3. Trial Design

This is a Phase 2 study listed as non-randomized, with no masking and a parallel model. The registry records enrollment of 8 and lists convalescent plasma as the intervention. Its stated aim was to observe clinical outcomes after transfusion and compare them with historical experience. The record does not describe a randomized allocation process or a masked assessment process.

The listed primary outcome concerns survival after treatment among severe, high-risk, and health care provider cohorts. Although the outcome title refers to Arms 1 and 2, the record does not provide a complete description of the arms or explain how participants were assigned to them. The arm descriptions are blank. It also does not provide the characteristics of any historical comparison group. Consequently, the record does not establish that the groups being compared were similar in baseline risk or care.

The study status is terminated. The recorded start date is 2020-07-14, and the primary completion date is 2021-09-14. These dates describe the registry record; they do not explain why the study was terminated or establish when each participant was treated or followed.

Non-randomized comparisons can be affected by differences between groups beyond the intervention. Historical experience may differ from study participants in patient characteristics, clinical practice, or the circumstances in which outcomes were recorded. The registry record does not report methods to address such differences. This design therefore does not support a like-for-like controlled comparison on the information available.

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

Analysis population for the primary outcome, as defined in the registry: no critical patients were enrolled.

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: No critical patients were consented for this study

6. Primary Endpoint

The registry lists the primary outcome as Arms 1 & 2: Number of COVID-19 Infected Patients in Severe, High Risk & Health Care Provider Cohorts Who Survive the Infection, measured over 30 days after initial treatment.

The primary endpoint is a count: the number of patients who survived COVID-19 infection after treatment on study. Its stated timeframe is 30 days after initial treatment, and its population is the severe, high-risk, and health care provider cohorts; the record notes that no critical patients were enrolled.

A survival count is a direct way to describe how many participants in a defined group were recorded as surviving during a specified follow-up period. Counts can be clinically interpretable, but a count alone does not show the chance of survival unless the number of participants eligible for the endpoint is also known. A comparison additionally requires clearly defined groups and an analysis that accounts for how those groups were formed.

The registry record lists one outcome measure but does not report the primary endpoint result, its denominator, or a comparative estimate. It therefore does not establish the observed survival count or the precision of any survival comparison. The outcome title refers to Arms 1 and 2, but arm-level outcome details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the primary outcome as a count of participants who survived infection after treatment. This is a binary-outcome setting at the participant level: each person is classified according to whether the specified event, survival, was recorded. A count is the number in a category, while an outcome rate or proportion also needs a clearly defined denominator. The primary outcome result and its denominator are not reported in the registry record, so neither can be interpreted from the posted information.

What can a confidence interval tell a reader?

In general, a confidence interval expresses uncertainty around an estimated quantity. A narrow interval indicates greater precision than a wide interval, under the assumptions of the method used. It does not by itself correct bias in study design, and it is not a guarantee that the true effect lies within the interval. No confidence interval for survival is reported in the registry record. Without a result and its uncertainty, the magnitude and precision of any comparison cannot be assessed.

Why does allocation matter?

Random allocation is one way to make comparison groups more similar, on average, with respect to measured and unmeasured characteristics. This study is listed as non-randomized. Its summary describes comparison with historical experience, but details of the historical group and the analysis are not reported. General statistical caution applies: groups formed at different times or by different processes may differ in prognosis, eligibility, clinical management, or outcome recording. Such differences can distort a treatment comparison. An adjustment model may address measured differences, but it cannot automatically remove bias from unmeasured differences. The record does not describe whether any adjustment was planned or performed.

What does the planning framework mean?

The registry's planning description characterizes sample-size calculations as illustrations based on an observed effect, not as the trial's own design. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning assumptions, not findings about the enrolled participants. The primary result and an observed effect are not reported in the registry record, and no analyses are listed. No numerical planning result or claim about achieved power can be inferred from the information recorded.

In general, a planning calculation estimates how much information a future study might need under its stated assumptions. It does not measure the probability that a completed study has detected a real effect. A calculation tied to an observed effect can also depend heavily on that estimate, particularly when the underlying study is small or the estimate is imprecise. Here, the registry record does not show the observed primary effect needed to evaluate the planning illustration.

What can a significance test establish?

In general, a significance test compares data with a specified null hypothesis under a model. A p-value describes how unusual data at least as extreme as those observed would be if that null hypothesis and the model assumptions held. It is not the probability that the null hypothesis is true, nor does it measure the clinical importance of an effect. No primary analysis or p-value is reported in the registry record. It would therefore be inappropriate to describe the outcome as statistically significant or not statistically significant.

These ideas do not substitute for a prespecified analysis plan. The registry record does not report the statistical analysis plan, any covariate adjustment, a method for handling the historical comparison, or the approach to missing outcomes. It also does not report interim analyses. The appropriate interpretation is limited to the design and endpoint information that is recorded, rather than assuming an unreported method was used.

The endpoint is a fixed-time survival count, not a time-to-event analysis as described in the registry. The record gives a follow-up timeframe of 30 days after initial treatment but does not describe event timing beyond that endpoint. General methods for time-to-event data would require information about timing and censoring; their use is not reported. The sample-size description distinguishes time-to-event calculations from other calculations, but it does not make this endpoint a time-to-event analysis.

Finally, statistical precision and validity are separate concerns. More observations can often improve precision, but they do not remove systematic differences between a study group and a historical comparator. Conversely, a valid design can still yield an imprecise estimate when little information is available. Because the primary result and its uncertainty are absent, neither precision nor the robustness of a treatment comparison can be judged from this record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Severe Patients", "High Risk", "Health Care Providers")
n      <- c(1, 6, 1)
events <- c(1, 6, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Severe Patients  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7
ARM  High Risk  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6
ARM  Health Care Providers  1  1  100.0  2.5  100.0  20.7  100.0  15.8  98.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure and no analyses. It does not report a statistical analysis plan, a hierarchy of outcomes, or procedures for handling multiple comparisons. The registry record therefore does not establish whether multiplicity was considered, whether other outcomes were analyzed, or what inferential adjustments might have been used. No adjustment should be assumed.

The primary endpoint result and its denominator are not reported. The record also does not describe missing outcome data, losses to follow-up, exclusions from analysis, or how such cases would be handled. It is therefore not possible to determine whether all enrolled participants contributed to the primary endpoint or whether the reported enrollment corresponds to the analysis population. The analysis populations and any rules for including participants are not reported in the registry record.

In general, missing outcomes can affect interpretation when the chance that an outcome is unobserved is related to participant characteristics or outcomes themselves. Statistical methods may make assumptions about missingness, but those assumptions need to be stated and assessed. No such assumptions or methods are reported. Similarly, multiple outcome testing can increase the chance of a false-positive finding if not addressed, but the absence of listed analyses means there is no reported set of tests on which to evaluate that issue.

These gaps do not establish that data were missing or that multiple testing occurred. They mean that the registry record does not provide enough information to assess either issue. Any detailed account of participant flow, analysis populations, or missing-data handling is not reported in the registry record.

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 5% reporting threshold.

The adverse-event record lists serious and other adverse events by group, along with deaths. For Severe Patients, the record lists 1 at risk, 0 with a serious event, 0 with another event, and 0 deaths. For High Risk, it lists 6 at risk, 0 with a serious event, 0 with another event, and 0 deaths. For Health Care Providers, it lists 1 at risk, 0 with a serious event, 0 with another event, and 0 deaths. Critical Patients is listed with 0 at risk and zero events and deaths.

These are recorded counts, not evidence that an event could not occur or that the intervention is free of risk. The registry record does not explain the adverse-event definitions, how events were collected, or whether follow-up was complete for safety reporting. The at-risk counts should not be treated as the primary endpoint denominators: the primary survival outcome result is not reported. The safety entries describe only the event counts recorded for these groups and do not establish a comparative safety effect.

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

The registry record establishes that a Phase 2, non-randomized study of convalescent plasma was registered, with survival 30 days after initial treatment as its primary outcome. It records enrollment of 8 and lists no statistical analyses. It also records that the study was terminated. These details describe the study record, but they do not supply the primary endpoint result.

The record does not report how many participants survived, a comparator result, an effect estimate, or an uncertainty interval. Thus, it cannot establish the size or direction of a survival difference. It cannot show whether any difference was measured precisely, nor whether an analysis found evidence against a null hypothesis. The absence of a reported result is not evidence that the outcome was favorable, unfavorable, or unchanged.

Even if outcome counts were available, the listed non-randomized design and historical comparison would require careful interpretation. Study participants and historical patients may differ in ways that affect survival. The registry record does not report the comparator details or analytical methods needed to evaluate those concerns. A simple contrast would not, on its own, demonstrate that the intervention caused an outcome difference.

The safety record reports zero serious adverse events, zero other adverse events, and zero deaths in the listed groups, with the stated at-risk counts. These observations should be read as recorded counts within the registry, not as proof of absence of risk. The record does not provide enough detail to assess how completely events were captured or how the safety groups relate to the primary analysis population.

In short, the record describes the question and design but does not provide results sufficient to answer the survival question. It supports no treatment recommendation and no conclusion that convalescent plasma did or did not change survival.

14. Why This Trial Matters Statistically

This trial illustrates a central distinction in clinical research: a clearly stated outcome is not the same as a reported result. The registry defines survival at 30 days after initial treatment as its primary measure, but does not report the survival count or an analysis. Without those data, readers cannot assess effect size, precision, or statistical evidence.

It also highlights the interpretive limits of non-randomized comparisons. The study summary refers to historical experience, while the record does not give detailed information about that comparator or how it was analyzed. Historical comparisons can be useful for context, but changes in patient mix, clinical care, or outcome recording can make groups incomparable. These issues are design limitations, not matters that can be settled by a p-value alone.

The small recorded enrollment and the absence of reported endpoint counts make it especially important not to overinterpret the safety counts as a complete account of outcomes. Zero recorded events in a group is a count, not a guarantee of zero risk. The registry does not describe event collection or follow-up completeness, so the scope of those observations cannot be evaluated.

Finally, the record shows why transparent reporting matters. Reporting denominators, group definitions, outcome counts, uncertainty intervals, analysis populations, and missing-data handling would allow readers to assess both the numerical findings and the assumptions behind them. Without those elements, the most defensible statistical conclusion is that the registry documents the study framework but does not provide enough outcome information to quantify its primary question.

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.

Several trial-specific details needed to interpret the primary outcome are not reported in the registry record. The arm descriptions are blank, and the record does not explain allocation to the arms named in the outcome title. It does not provide arm-specific enrollment, baseline characteristics, or the definition and characteristics of the historical experience used as the stated comparator. These omissions limit assessment of comparability and of who contributed to each group.

The record lists a primary survival outcome and its timeframe, but does not give the outcome count, denominator, effect estimate, uncertainty interval, or analysis. It does not describe follow-up completeness or whether deaths and other outcomes were ascertained consistently. The statistical analysis plan, model specifications, adjustment methods, and handling of missing data are not reported in the registry record.

The study is listed as terminated, but the reason for termination is not reported. The recorded dates and enrollment do not explain whether the planned study objectives were completed or why no analyses are listed. No sample-size justification for the trial's own design is reported. The planning description is explicitly an illustration rather than a design justification, and the primary observed effect needed to interpret such an illustration is not reported.

Safety interpretation is also limited by the lack of event definitions, collection methods, and follow-up details. The recorded zero counts are descriptive entries and cannot establish that all relevant events were captured. Together, these reporting gaps mean the record is insufficient for a quantitative assessment of survival or for a robust comparison with historical experience.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Use of Convalescent Plasma for COVID-19 — NCT04408040.
• Registry record last updated 2022-11-14; status last verified 2022-10.
• Results first posted 2022-11-14.
• 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

NCT04408040 is a Phase 2, non-randomized, unmasked, parallel study sponsored by Northside Hospital, Inc. The registry lists convalescent plasma as the intervention and COVID as the condition. Enrollment is recorded as 8. The recorded start date is 2020-07-14, the primary completion date is 2021-09-14, and the study status is terminated.

The primary outcome is the number of participants in severe, high-risk, and health care provider cohorts who survived infection 30 days after initial treatment; the record says no critical patients were enrolled. The study summary describes comparison with historical experience. The registry lists one outcome measure and no analyses, and does not report the primary outcome result or detailed comparator methods.

Safety entries list zero serious events, zero other events, and zero deaths in the reported groups. These counts are descriptive and do not replace the missing primary outcome analysis.