This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Phase II Study of Intravenous Immunoglobulin (IVIg) for Alzheimer's Disease (NCT00299988), a randomized phase 2 study. The primary outcome is ADAS-Cog.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00299988 |
| Phase | Phase 2 |
| Condition | Alzheimer's Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 24 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Weill Medical College of Cornell University |
| Results posted | Yes |
2. Clinical Question
Population
People with mild to moderate Alzheimer’s disease who were capable of giving informed consent were the intended study population. The registry record lists Alzheimer’s disease as the condition and an enrollment of 24. It does not report further participant characteristics, such as age distribution, baseline cognitive scores, or other eligibility details.
Intervention
The intervention was intravenous immunoglobulin (IVIg), identified in the official title as Gammagard. The brief summary describes four IVIg dosing regimens during a six-month placebo-controlled period. The specific doses and how participants were distributed among those regimens are not reported in the registry record.
Comparator
The comparator was saline placebo. The brief summary describes random assignment to IVIg or placebo, with a planned allocation of 16 patients to IVIg and 8 to placebo. The registry record also lists IVIG and Placebo outcome groups with those group sizes, but provides no primary outcome values for either group.
Primary question
The primary outcome was ADAS-Cog, a measure of cognitive symptoms, with a registry timeframe of 12 months. The central comparison is whether the reported mean ADAS-Cog outcome differs between the IVIg and placebo groups. The registry record does not provide the group means, confidence intervals, or an estimable two-arm comparison, so it does not answer that question with a numerical treatment-effect estimate.
3. Trial Design
The registry describes a randomized, quadruple-masked, parallel-group Phase II study. Its official title identifies it as placebo-controlled and double-blind, while the registry’s masking classification is quadruple. These labels describe the record’s design entries; the registry record does not explain which roles were masked or provide further masking procedures. The study was sponsored by Weill Medical College of Cornell University.
The registry enrollment is 24. In the brief summary, 24 patients were to be randomly assigned to IVIg or saline placebo for six months, with 16 assigned to IVIg and 8 to placebo. The outcome record lists IVIG and Placebo groups of 16 and 8, respectively. Four IVIg dosing regimens are mentioned, but their doses, allocation details, and relationship to the reported IVIG group are not reported in the registry record.
The brief summary describes cognitive, behavioral, and functional assessments at baseline, three months, and six months. It also describes blood collection around infusions, lumbar punctures before and after six months, and PET imaging substudies at two time points. These are planned procedures in the summary; their completion and results are not reported in the registry record.
The summary further describes an opportunity to receive IVIg for an additional 12 months after the initial placebo-controlled period. The primary ADAS-Cog outcome has a registry timeframe of 12 months, but the relationship between that timeframe and the six-month placebo-controlled period and extension is not explained. The study status is TERMINATED. The reason for termination and the timing of termination are not reported in the registry record. The recorded start is 2006-02 and primary completion is 2009-01.
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
| Stage | IVIG | Placebo |
|---|---|---|
| STARTED | 16 | 8 |
| COMPLETED | 16 | 8 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | IVIG | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 16 | 8 | 24 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 16 | 8 | 24 |
| Age, Categorical: >=65 years | Participants | 0 | 0 | 0 |
| Sex: Female, Male: Female | Participants | 9 | 4 | 13 |
| Sex: Female, Male: Male | Participants | 7 | 4 | 11 |
| Region of Enrollment: United States | Participants | 16 | 8 | 24 |
6. Primary Endpoint
The registry lists the primary outcome as ADAS-Cog, measured over 12 months.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is ADAS-Cog, the Alzheimer’s Disease Assessment Scale-Cognitive Subscale. The registry describes it as a neuropsychological assessment used to assess the severity of cognitive symptoms of dementia. It gives the scale range as 0 to 70 and states that higher scores indicate greater cognitive dysfunction. The record describes ADAS-Cog as widely used in cognitive clinical trials and as a measure used to assess antidementia treatments.
As a continuous measure, ADAS-Cog can be summarized by a group mean. Comparing means can describe the average difference in measured cognitive symptoms between treatment groups, while a confidence interval conveys uncertainty around an estimate. Those are general statistical interpretations, not a result for this trial: the registry record contains no mean or confidence interval for either group, and the two-arm comparison is not estimable from the posted outcome data.
The registry lists the primary outcome timeframe as 12 months. The brief summary describes assessments during the six-month placebo-controlled period and an additional 12-month extension opportunity. Whether the primary outcome refers to the extension, another follow-up point, or a different analysis timing is not reported in the registry record. That distinction matters when interpreting the intended contrast, because a measurement during continued placebo control and one after an extension need not represent the same comparison.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies ADAS-Cog as the primary outcome and reports a 12-month timeframe, but neither group has a posted mean, spread, or confidence interval. The registry also indicates that values are missing or not estimable for a two-arm comparison of this continuous endpoint. As a result, there is no numerical estimate of the difference between IVIg and placebo to interpret. The direction, size, and precision of any treatment effect are not reported in the registry record.
This absence is not evidence that the groups had the same outcome, nor does it establish that one group did better. It means that the posted record does not permit that comparison. Without group estimates or a sponsor-reported analysis, it is not possible to assess how the observed ADAS-Cog results varied within groups, how uncertain a difference might be, or whether any analysis adjusted for baseline values or other factors. Those details are not reported in the registry record.
The registry lists 16 participants in the IVIG outcome group and 8 in the Placebo outcome group, but those group sizes do not supply the missing outcome measurements. A group size alone cannot show the average outcome or its variability. Nor can the stated overall enrollment replace those statistics. The posted results include no analyses, and no secondary outcomes are posted. The registry record does not report why the study was terminated or whether the primary endpoint data were collected, analyzed, or withheld.
The timepoint also needs care. The primary endpoint is labeled at 12 months, while the summary describes a six-month placebo-controlled period followed by an extension in which participants could receive IVIg for an additional 12 months. The record does not clarify how the 12-month endpoint relates to that schedule, or which treatment contrast was intended at that time. It would be inappropriate to infer that the outcome compares the original randomized groups under continuing placebo control.
The appropriate statistical conclusion is therefore limited: the registry records the endpoint and group sizes but does not provide an interpretable ADAS-Cog treatment-effect estimate. No conclusion about benefit, lack of benefit, or equivalence can be drawn from these missing outcome values. The absence of an estimate also means that no confidence interval can be used to distinguish a narrowly estimated effect from a highly uncertain one.
9. Statistical Methods Explained
The primary outcome is continuous, and its stated summary parameter is a mean. In general, a mean represents the average measured score in a group. A comparison of group means can describe the average separation between treatment groups, but it does not describe every participant’s experience or the full distribution of scores. Interpreting a mean comparison requires the actual group estimates and information about their uncertainty. Neither is available for this endpoint in the registry record.
What does a confidence interval communicate?
In general, a confidence interval expresses the uncertainty associated with an estimated quantity under a specified statistical procedure. For a treatment comparison, it helps readers assess which effect sizes are compatible with the data and the analysis. A narrow interval indicates greater precision than a wide interval, while an interval spanning effects in different directions may leave the direction uncertain. These general principles cannot be applied to the trial’s ADAS-Cog comparison because the registry reports no group confidence intervals and no estimable contrast.
The registry identifies the primary outcome’s dispersion as a 95% confidence interval, but does not provide interval limits. The record also does not clarify whether the intended interval describes each group mean or a between-group effect. Even if group-level intervals had been present, they would not by themselves replace a directly reported comparison; the statistical uncertainty of a difference should be assessed using the comparison’s own estimate and interval. No such estimate is posted.
Why is the two-arm comparison unavailable?
The registry’s outcome information states that values are missing or not estimable for a two-arm comparison of this continuous endpoint. The record lists group sizes but leaves the outcome values and limits blank. A mean difference cannot be reconstructed from group sizes alone. A simple unadjusted recalculation would also require the relevant outcome summary statistics, which are not present. No recalculated treatment effect is therefore available, and there is no sponsor analysis in the registry record to take precedence over a recalculation.
In general, random assignment is intended to support a fair comparison by making treatment assignment independent of participants’ baseline characteristics, subject to the conduct of the study and the analysis. The registry describes randomization, but does not report sequence generation, allocation concealment, adherence, or the characteristics of participants in each group. Those implementation details cannot be assessed from the posted information.
What can be said about the planning assumptions?
The record’s description of planning illustrations specifies 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. It also specifies that non-time-to-event illustrations are expressed as participants per arm. These are planning assumptions, not evidence about the trial’s results or its original design. The registry record does not report the trial’s own sample-size justification or provide an observed effect from which to evaluate such planning. A planning sample size is not observed power and does not establish whether the study’s data would be conclusive.
In general, a two-sided test considers departures in either direction rather than prespecifying only an increase or decrease. A normal approximation uses a mathematical reference distribution to estimate uncertainty or plan a study. Equal allocation is a planning arrangement that assigns the same number of participants to each group; it differs from the registry’s stated planned allocation of 16 to IVIg and 8 to placebo. The planning description should not be mistaken for a report that this trial used equal allocation.
Why does variability matter?
For a continuous outcome, the spread of individual scores affects the precision of a mean and a group comparison. In general, greater variability makes it harder to distinguish an underlying treatment contrast from random variation, whereas lower variability can yield more precise estimates when other features are comparable. No score spread is posted for ADAS-Cog, so the outcome variability and its contribution to uncertainty cannot be assessed. The registry’s general designation of the outcome as a mean with a confidence interval does not substitute for the missing numerical results.
The record does not describe the analysis model, covariate adjustment, assumptions about the score distribution, or handling of repeated measurements. It also does not report an analysis population or a method for missing outcomes. These omissions prevent assessment of whether the intended analysis used all randomized participants, a subset, or another population, and whether the analysis accounted for repeated measurements or other features of the design. The posted outcome record is not enough to identify an analysis procedure beyond the mean and confidence-interval description.
Finally, the registry lists no analyses. It does not report a test statistic, p-value, treatment-effect estimate, or interval for the primary comparison. Statistical significance cannot be assessed from the available endpoint record, and a missing p-value should not be interpreted as a nonsignificant result. The central limitation is more basic: the numerical outcome information needed to estimate the comparison is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The study description includes cognitive, behavioral, and functional measures, and mentions biological sampling and PET imaging substudies. The registry lists two outcome measures but no secondary outcomes are posted, and it lists no analyses. It does not identify the second outcome measure in the information available for interpretation here, nor report which outcomes were formally designated secondary or how they were analyzed.
In general, evaluating multiple outcomes, timepoints, or treatment regimens can create multiplicity: the more comparisons considered, the greater the chance that an apparently notable finding arises by chance if results are interpreted without an appropriate plan. Researchers may address multiplicity through prespecified outcome hierarchies, adjustment procedures, or cautious interpretation. The registry record does not report a multiplicity strategy, a testing hierarchy, or whether analyses were prespecified. The mention of four IVIg dosing regimens and assessments at several timepoints does not establish which comparisons were planned or conducted.
The registry does not report missing-data methods, reasons for missing observations, or the number of participants contributing ADAS-Cog data at the stated timeframe. It also does not report an analysis population, such as whether the primary analysis was intended to include all randomized participants. These details are important because exclusions and missing outcome measurements can affect the groups being compared and the uncertainty of an estimate.
The outcome’s 12-month timeframe is not reconciled with the six-month placebo-controlled period and the extension described in the summary. The registry record does not explain whether the analysis was based on the original assignment, how extension participation was handled, or which participants were included at that timepoint. Without those details, the target contrast and the handling of post-period treatment cannot be established from the record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| IVIG | 0 | 16 | 0.0% |
| Placebo | 0 | 8 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| IVIG | 10 of 16 |
| Placebo | 4 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| IVIG | 0 of 16 |
| Placebo | 0 of 8 |
The registry lists serious adverse events for the IVIG group as 0 affected among 16 at risk, and for the Placebo group as 0 affected among 8 at risk. It also lists other adverse events as 0 affected among 16 at risk for IVIG and 0 affected among 8 at risk for Placebo. No serious adverse event terms are listed. These entries describe the registry’s posted counts; they do not provide event descriptions or further detail about collection and reporting.
Deaths are listed separately: 10 in the IVIG group and 4 in the Placebo group. The record does not report causes of death, timing, relationship to treatment, or how these death counts relate to the adverse-event categories. The counts should not be treated as evidence that treatment caused or prevented deaths. The registry also does not explain the follow-up period underlying the death entries or whether the counts cover the same period as the adverse-event entries.
In general, safety counts require context about how events were defined, collected, and followed over time. Counts alone do not establish a comparative risk, and no rate or treatment comparison is calculated. The registry record does not report additional safety analyses or explanations that would resolve these limitations.
12. What the Result Does, and Does Not, Mean
The registry record establishes that this was a randomized Phase II study of IVIg versus saline placebo for mild to moderate Alzheimer’s disease, with ADAS-Cog designated as the primary outcome. It also records group sizes and safety counts. However, the primary outcome values and an estimable comparison are absent. Consequently, the posted results do not quantify the difference in cognitive scores between the groups or the uncertainty around such a difference.
This is not a finding that IVIg and placebo had identical outcomes. It is also not evidence that IVIg was superior or inferior. Those conclusions require interpretable outcome estimates and a valid comparison. No p-value, treatment-effect estimate, or confidence interval for the primary outcome is reported in the registry record. The absence of these results leaves the central efficacy question unanswered by the posted data.
The safety entries also need a narrow reading. The registry lists no affected participants for its serious and other adverse-event categories, alongside death counts for both groups. It provides no timing, causes, event terms, or explanation of how the categories relate. These entries cannot establish a treatment-related safety effect or explain the deaths.
Study status is TERMINATED, but the reason is not reported in the registry record. The record does not establish whether termination followed safety concerns, logistical issues, recruitment, or another reason, and no such explanation should be inferred. It also does not make clear how the 12-month primary outcome timeframe relates to the six-month placebo-controlled period and the described extension. These gaps limit interpretation of both the intended comparison and the completeness of the posted outcome record.
Overall, the posted information supports a description of the design and what outcomes were intended, but not an estimate of the primary treatment effect. Missing results should be distinguished from evidence of no effect. Any conclusion about efficacy, equivalence, or comparative safety would go beyond what the registry record reports.
13. Why This Trial Matters Statistically
This trial illustrates a basic distinction in clinical-trial interpretation: a design description is not the same as an analyzable result. Randomization, masking, a comparator, and a defined endpoint describe how a study was intended to generate evidence. To evaluate the treatment contrast, readers also need outcome estimates and a measure of uncertainty. The registry records the former design features but does not report the ADAS-Cog values or an estimable comparison.
It also demonstrates why group sizes alone cannot answer a clinical question. The record lists 16 participants in the IVIG outcome group and 8 in the Placebo group, but without outcome means and variability those counts cannot reveal the average score difference or how precise it might be. In general, sample size and outcome data work together in an estimate; neither replaces the other.
The discrepancy between the stated 12-month endpoint timeframe and the summary’s six-month placebo-controlled period followed by an extension also highlights the importance of a clearly defined estimand: the precise treatment contrast, population, outcome, and timepoint a result is intended to describe. The registry record does not resolve how those time descriptions connect, so the intended 12-month comparison cannot be specified with confidence.
Finally, a terminated study with no posted analysis underscores the difference between absence of evidence and evidence of absence. The record does not support a numerical conclusion about ADAS-Cog, and it does not explain why the study ended. For clinical researchers and statisticians, that makes transparent outcome reporting and a clear account of analysis populations, missing data, and timing essential to judging what a trial can establish.
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 principal limitation for interpreting this particular trial is that the registry has no primary ADAS-Cog estimates or confidence intervals for either treatment group. It explicitly indicates that the continuous two-arm comparison is missing or not estimable. Without these quantities, the effect’s magnitude, direction, and precision cannot be evaluated. The registry lists no analyses and no secondary outcomes, so there is no posted alternative outcome analysis to contextualize the missing primary comparison.
The endpoint timeframe is recorded as 12 months, while the brief summary describes a six-month placebo-controlled period and an additional 12-month extension opportunity. The registry does not explain how these periods map to the primary analysis, whether the comparison remains between the original randomized assignments, or how extension treatment is represented. That ambiguity limits interpretation of the endpoint even apart from the absent numerical results.
The record mentions four IVIg dosing regimens but does not report the doses, their allocation, or whether dose-specific outcomes were analyzed. It also does not report baseline characteristics, adherence, participant flow, reasons for missing observations, missing-data procedures, analysis populations, model specification, or multiplicity handling. These omissions prevent assessment of balance, attrition, and the analysis choices that could affect inference.
The study is marked TERMINATED, but the reason and circumstances are not reported in the registry record. Safety information is limited to counts, with no reported causes or timing for deaths and no listed serious adverse-event terms. Thus, neither the missing efficacy comparison nor the safety entries can be given a fuller interpretation from this record alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase II Study of Intravenous Immunoglobulin (IVIg) for Alzheimer's Disease — NCT00299988.
- Registry record last updated 2019-12-11; status last verified 2019-11.
- Results first posted 2019-12-11.
- 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.
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18. Record Summary
The registry describes NCT00299988 as a randomized, quadruple-masked, parallel-group Phase II study of IVIg versus saline placebo for mild to moderate Alzheimer’s disease. It lists enrollment of 24, a planned six-month placebo-controlled period, and a possible extension. ADAS-Cog is the primary outcome, with a stated timeframe of 12 months.
The outcome record lists IVIG and Placebo groups of 16 and 8, but provides no ADAS-Cog means or confidence intervals and no estimable two-arm comparison. No analyses or secondary outcomes are posted. Serious and other adverse-event counts are listed as zero affected in both groups; deaths are listed as 10 for IVIG and 4 for Placebo, without further explanation. The study status is TERMINATED. The reason for termination and the relationship between the primary endpoint timeframe and the described study periods are not reported in the registry record.