Effect of IVIG on Cerebral and Retinal Amyloid in Mild Cognitive Impairment Due to Alzheimer Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of IVIG on Cerebral and Retinal Amyloid in Mild Cognitive Impairment Due to Alzheimer Disease (NCT03319810), a na phase 2 study. The primary outcome is Change in Baseline Standard Uptake Ratio Values (SUVr) of Florbetapir PET at 3 Months.

2. Clinical Question

This is a proof-of-concept question, focused on whether a measurable change in a brain imaging marker might be evident after the intervention. The study description also mentions retinal scanning, but the listed primary endpoint is the change in Florbetapir PET SUVr. A planned measurement is not itself evidence that a change occurred: interpretation depends on the observed values, their variability, and how missing observations were handled. Those outcome details are not reported in the registry record.

Because the study has no concurrent control group, any change from baseline would be a within-group observation. It could describe what happened over time in the enrolled group, but by itself it could not distinguish an intervention-associated change from other explanations, such as measurement variability or changes that might have occurred over time without treatment.

3. Trial Design

The registry lists this as a Phase 2, completed, single-group study sponsored by Sutter Health. Its recorded start date is 2018-01-04 and its primary completion date is 2018-07-19. Enrollment is recorded as 5. These entries describe the trial record; they do not establish how many participants contributed data to the primary endpoint.

The intervention is listed as Octagam 10%, a biological intervention. The study description specifies IVIG at 0.4 g/kg every 14 days x 5 infusions. The arm is described as infusion of IVIG. No second arm or control condition is listed. Allocation is NA, and masking is none, consistent with the record's single-group classification rather than a randomized, blinded comparison.

The primary outcome is a continuous imaging measure: change in baseline standard uptake ratio values (SUVr) of Florbetapir PET at 3 months. The stated timeframe is baseline to 3 months, and the outcome is characterized by a mean and standard deviation. The description explains that SUVr is used to quantify each participant's amyloid burden. Although the study summary also mentions retinal scanning, the primary endpoint listed in the record is the PET measure.

The registry status is completed, but completion status is not the same as a posted analysis. The record lists 2 outcome measures and 0 analyses. It does not report the primary endpoint's numerical estimate, its standard deviation, a confidence interval, or a test result. Further details about eligibility, the conduct of imaging assessments, adherence, and participant flow are not reported in the registry record.

The lack of a control arm matters when interpreting any before-and-after result. A baseline-to-follow-up change could be described for the treated group, but it would not estimate a randomized treatment contrast. In addition, the small recorded enrollment means that any group-level estimate would need to be read with attention to its uncertainty; the precision cannot be evaluated without the posted outcome data.

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

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 Baseline Standard Uptake Ratio Values (SUVr) of Florbetapir PET at 3 Months, measured over Baseline to 3 months.

The primary endpoint is change from baseline in standard uptake ratio values (SUVr) measured with Florbetapir PET at 3 months. SUVr is described in the registry as a way to quantify an individual's amyloid burden. The endpoint therefore uses an imaging measure rather than a direct clinical measure of cognition or daily function. The study description frames brain amyloid as relevant to cognitive decline and conversion to Alzheimer disease, providing the biological rationale for measuring this marker.

Expressing the endpoint as change over time focuses the question on whether the PET measure differs between baseline and the follow-up assessment. The registry specifies the summary as a mean with standard deviation, which describes the group average change and the spread of individual changes. A mean alone would not show whether changes were similar across participants or whether the group result was influenced by a small number of observations. The standard deviation helps describe variability, while an interval estimate would be needed to show uncertainty in the mean.

The endpoint description does not establish that SUVr is a validated substitute for a clinical benefit, nor does a change in an imaging marker alone establish a change in symptoms. The record gives no numerical outcome result, so the direction, magnitude, and precision of any change cannot be assessed. It also does not report details of image processing, the regions used in the ratio, or how incomplete scans were handled.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary outcome summarized as a mean and standard deviation. Those are descriptive statistics: the mean represents the average change in SUVr for the observations included in an analysis, while the standard deviation describes how dispersed individual changes are around that average. The two quantities answer different questions. A mean gives a central summary; a standard deviation helps show whether participant-level changes were tightly grouped or varied substantially.

What does a change score represent?

A change score compares an individual's follow-up measurement with that individual's baseline measurement. The group summary then describes the changes across participants with usable measurements. This approach can account for baseline differences between individuals when describing within-person change, but it does not create a control group. General statistical explanation: change scores can also be affected by measurement error at either assessment, and the interpretation depends on the timing and consistency of measurements.

The registry specifies the interval as baseline to 3 months and identifies the measure as Florbetapir PET SUVr. It does not report individual baseline or follow-up values, the mean change, or the standard deviation. Thus, the registered summary format is known, but no numerical descriptive estimate can be interpreted. It is also not reported in the registry record whether the analysis used paired observations only, how images were processed, or what happened when a participant lacked a usable scan.

Why does uncertainty matter?

An estimated mean is subject to sampling variability: another group drawn from the same target population could produce a different estimate. A confidence interval is a range of values compatible with the observed data and the stated statistical method, and its width indicates the estimate's precision. A narrow interval indicates greater precision than a wide interval, while neither width nor location alone resolves limitations in study design. No confidence interval is reported in the registry record, so the uncertainty around any mean change cannot be assessed.

A hypothesis test, when used, assesses how compatible the observed data are with a specified null model under its assumptions. A p-value does not measure the probability that a treatment works, and it does not tell the reader how large or important an effect is. The registry record lists 0 analyses and does not report a test or p-value. The statistical plan, including any model assumptions or inferential procedures, is not reported in the registry record.

What does the design allow?

Because this is a single-group study, any primary analysis would be a within-group assessment unless another comparison not described in the record was used. General statistical explanation: a control group helps account for changes that could occur over time independently of the intervention. Without that comparator, a change from baseline cannot isolate a treatment effect. The record's allocation entry is NA, and masking is listed as none; a randomized comparison should not be inferred.

The outcome is continuous, and the registered summary uses the mean and standard deviation. General statistical explanation: methods for continuous outcomes often rely on assumptions about the distribution of observations or model residuals. Departures from those assumptions, influential observations, and small samples can affect estimates and uncertainty. The record does not identify the method used to assess or address such issues. It also does not report a statistical analysis plan, any covariate adjustment, or a prespecified threshold for interpreting the endpoint.

How should planning calculations be read?

The study's sample-size assumptions describe a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The record says the effect to detect is a stated fraction of the observed effect, and that non-time-to-event planning results are expressed as participants per arm. These are hypothetical planning assumptions, not evidence about the trial's observed power. They do not describe the registered single-group design, which has no two-arm allocation. No numerical planning result is reported in the registry record for interpretation in this analysis.

In general, a planning calculation estimates the sample size needed under specified assumptions; it does not prove that a completed study had adequate power or that an effect was present. Calculations tied to an observed effect can also depend on the stability of that estimate. Here, the primary outcome estimate itself is not reported, and the planning illustration's two-arm assumptions do not match the study's listed design. Accordingly, those assumptions cannot substitute for a reported outcome analysis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Infusion of IVIG")
n   <- c(5)
m   <- c(-3.83)
sp  <- c(2.84)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Infusion of IVIG  5  -3.830  2.840  -7.356  -0.304

11. Multiplicity, Missing Data and Analysis Populations

The record lists 2 outcome measures, but it does not describe a multiplicity adjustment or explain how the outcomes were prioritized in the analysis. The primary endpoint is identified as change in baseline Florbetapir PET SUVr at 3 months. The registry record does not report whether any additional outcome was treated as secondary, exploratory, or part of a family of tests. It also does not report a statistical analysis plan, so the intended handling of multiple outcomes or repeated analyses is not known.

General statistical explanation: when several outcomes or tests are examined, the chance of at least one apparently unusual result can increase if each is assessed separately without accounting for the number of tests. Multiplicity procedures are used in some analyses to control this issue. Whether such an adjustment is needed, and which approach is appropriate, depends on the prespecified questions and analysis plan. Those details are not reported in the registry record, so no conclusion about multiplicity control can be drawn.

Missing-data methods and analysis populations are also not reported in the registry record. The record does not state how many participants had evaluable baseline and follow-up PET scans, whether all enrolled participants were included in the primary analysis, or how incomplete observations were handled. It does not describe an intention-to-treat population, a per-protocol population, imputation, or sensitivity analyses. These terms should not be assumed to apply merely because the study has a registered endpoint.

General statistical explanation: missing outcome data can affect both the size and the reliability of an estimate, particularly if the chance of missingness is related to participant characteristics or outcomes. A clear account of analyzed participants and missing-data assumptions is needed to judge robustness. In the absence of those details and of a posted endpoint result, the completeness and analysis basis of any primary estimate cannot be evaluated.

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 non-serious adverse event terms

The registry's safety figures list 5 participants at risk for serious adverse events and 0 affected by a serious adverse event. For other adverse events, it lists 5 at risk and 1 affected. The record lists 0 deaths. These are the posted counts for the IVIG group; they do not provide event descriptions or establish whether an event was judged related to the intervention.

The categories should be read as reported, not combined. The record provides no serious adverse event terms, and the list of top serious terms is empty. The single other adverse event is not described in the registry record for this analysis. The figures do not show the timing, severity, duration, or outcome of that event, or whether any participant experienced more than one event.

These counts are descriptive safety information from a small single-group study, not a comparative estimate of risk. With no control group, they cannot show how the event counts compare with another treatment or with no intervention. They also do not establish the absence of unreported or unrecorded events. The safety entries should not be interpreted as proof of safety or harm; they report only the counts and categories recorded in the registry.

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

The registry record establishes that a completed Phase 2, single-group study was designed to examine IVIG and a brain amyloid imaging measure in mild cognitive impairment due to Alzheimer disease. It identifies Florbetapir PET SUVr change from baseline to 3 months as the primary endpoint and describes a regimen of 0.4 g/kg every 14 days x 5 infusions. It also records enrollment of 5 and the posted adverse-event counts.

The record does not provide the numerical primary endpoint result. It therefore cannot show whether average SUVr changed, the direction or magnitude of any change, or how precisely a change was estimated. No statistical analysis is listed. The fact that the study is marked completed does not supply those missing results, and the planned use of a biomarker does not establish that the marker changed.

Even if a within-group change were reported, the design would not support a direct comparison with an untreated or placebo group. General interpretation: changes over time can reflect influences other than the intervention, including measurement variation and natural temporal change. A single-group before-and-after result can describe the observed course in that group, but cannot by itself identify the intervention as the cause.

The endpoint is an imaging biomarker, not a reported clinical outcome. The registry description gives a rationale for measuring amyloid burden, but does not establish that a change in SUVr corresponds to a change in cognition, function, or other patient experience. The retinal scan mentioned in the study summary also has no numerical result in the registry record.

Accordingly, the record supports conclusions about the study's design and registered question, but not about the direction, size, precision, clinical meaning, or cause of a primary endpoint change. The safety counts are likewise descriptive and lack a comparator. Any broader interpretation would require outcome data and analysis details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically notable because its registered question is a within-group change in an imaging biomarker, while the design has no concurrent control. That distinction is central: an observed change over time is a descriptive finding, whereas estimating an intervention effect requires a comparison that helps separate treatment-related change from other explanations. The record's single-group classification, allocation listed as NA, and masking listed as none define important limits on causal interpretation.

The study also illustrates the difference between a registered endpoint and a reported result. The primary measure, timeframe, and summary type are specified, but the record lists 0 analyses and does not provide a numerical estimate. Without an estimate and its uncertainty, readers cannot assess the direction, magnitude, or precision of the result. A completed status does not resolve this gap.

Use of a biomarker raises a separate interpretive question. A measure can be relevant to a biological hypothesis without automatically serving as evidence of a clinical effect. The registry explains the rationale for quantifying amyloid with SUVr, but the record does not report a clinical outcome result or explain how a biomarker change should be interpreted in relation to patient experience.

Finally, a small recorded enrollment makes transparent reporting of participant flow, missing scans, and analysis methods especially important for assessing precision and representativeness. Those details are not reported in the registry record. The trial therefore provides a useful example of why design, endpoint selection, result reporting, and uncertainty must be considered together rather than treating a registered measurement as an established finding.

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 most immediate limitation for interpretation is that no numerical primary endpoint result or analysis is reported. Mean change, standard deviation, confidence interval, and test results are not available in the registry record. The endpoint's direction, magnitude, and precision therefore cannot be described.

The study is single-group, with no concurrent control. This limits causal interpretation of any possible change from baseline. Masking is listed as none, and allocation is listed as NA. The record does not report additional procedures that might reduce measurement or assessment bias.

Enrollment is recorded as 5, but participant flow and the number with evaluable PET scans are not reported in the registry record. The handling of missing observations, exclusions, and analysis populations is also not reported. Without those details, the population represented by a possible endpoint estimate cannot be established.

The registry identifies a PET endpoint but does not provide details of imaging acquisition, image processing, regions of interest, or quality-control procedures. It mentions retinal scanning in the study summary, but no retinal result is given in the registry record for this analysis. The relationship between that measurement and the primary endpoint is not reported.

The analysis plan, multiplicity approach, assumptions, covariate adjustments, and sensitivity analyses are not reported in the registry record. The record also does not provide detailed participant characteristics or explain the applicability of the findings beyond the enrolled group. These gaps limit assessment of internal validity, robustness, and generalizability. The posted safety counts are descriptive and lack a comparator or event-level detail, which further limits comparative safety interpretation.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effect of IVIG on Cerebral and Retinal Amyloid in Mild Cognitive Impairment Due to Alzheimer Disease — NCT03319810.
• Registry record last updated 2019-06-25; status last verified 2019-06.
• Results first posted 2019-04-16.
• 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

NCT03319810 is a completed Phase 2, single-group study sponsored by Sutter Health. The recorded start date is 2018-01-04, and the primary completion date is 2018-07-19. Enrollment is listed as 5. The intervention is Octagam 10% IVIG, described as 0.4 g/kg every 14 days x 5 infusions.

The primary endpoint is change in Florbetapir PET standard uptake ratio values (SUVr) from baseline to 3 months, summarized by a mean and standard deviation. The study summary also mentions retinal scanning. The registry lists 2 outcome measures and 0 analyses; no numerical primary endpoint result is reported.

For the IVIG group, the registry lists 0 serious adverse events among 5 at risk, 1 other adverse event among 5 at risk, and 0 deaths. Event descriptions and a concurrent comparison are not reported.