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 A Pilot Trial of Interferon Beta-1a in Alzheimer's Disease (NCT01075763), a randomized phase 2 study. The primary outcome is Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01075763 |
| Phase | Phase 2 |
| Condition | Alzheimer's Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 42 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Merck KGaA, Darmstadt, Germany |
| Results posted | Yes |
2. Clinical Question
Population
People with early-onset Alzheimer's disease were the intended study population. The brief summary describes a 52-week study conducted in 40 subjects, while the registry enrollment field lists 42. The primary endpoint population is described separately as the per protocol population: participants who received treatments as scheduled and were followed up to week 52.
Intervention
The treatment arm received subcutaneous interferon beta-1a (Rebif® 22 microgram, three times per week). The study was described as evaluating safety, tolerability and clinical efficacy.
Comparator
The comparator was placebo. The registry identifies a randomized, double-masked, parallel-group design, but does not report further details about the randomization procedure or who was masked.
Primary question
The primary outcome was the mean ADAS-Cog score at baseline and Week 52 in the per protocol population. The study aimed to compare neuropsychological performance changes from screening/baseline to Week 52 between the treatment and placebo arms. Numerical outcome results and the estimated between-arm difference are not reported in the registry record, so the size and precision of any difference cannot be described.
3. Trial Design
The registry identifies this as a randomized, double-masked, parallel-group phase II pilot trial of interferon beta-1a in Alzheimer's disease. The study was multicentric and compared a Rebif® treatment arm with a placebo arm. The treatment description specifies subcutaneous interferon beta-1a at 22 microgram three times per week. The brief summary describes a 52-week study; the primary outcome timeframe is baseline and Week 52.
The registry lists enrollment as 42, whereas the brief summary says the study was conducted in 40 subjects. These figures are not reconciled in the registry record. The primary outcome population is defined as per protocol: participants who received treatment as scheduled and were followed up to week 52. The record does not report how many participants were included in that analysis or how the per protocol population was selected beyond this definition.
The study start is recorded as 2004-11 and primary completion as 2008-05; its status is completed. The sponsor is Merck KGaA, Darmstadt, Germany. The registry does not report the random sequence generation method, allocation concealment, masking procedures, or details of the participating centers. It also does not state the planned sample-size justification or provide enough design information to determine how the pilot study's size was chosen.
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 | Rebif 22 Mcg | Placebo |
|---|---|---|
| STARTED | 23 | 19 |
| COMPLETED | 19 | 15 |
| NOT COMPLETED | 4 | 4 |
Reasons for not completing this period:
| Reason | Rebif 22 Mcg | Placebo |
|---|---|---|
| Lost to Follow-up | 2 | 1 |
| Lack of Efficacy | 0 | 1 |
| Withdrawal by Subject | 2 | 2 |
Analysis population for the primary outcome, as defined in the registry: Per protocol population included all participants who received treatments as scheduled and were followed up to week 52.
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 | Rebif 22 Mcg | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 23 | 19 | 42 | |
| Age, Continuous | years | 63.00 (SD 9.08) | 64.58 (SD 6.41) | 63.71 (SD 7.87) |
| Sex: Female, Male: Female | Participants | 15 | 11 | 26 |
| Sex: Female, Male: Male | Participants | 8 | 8 | 16 |
6. Primary Endpoint
The registry lists the primary outcome as Alzheimer's Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) Score, measured over Baseline and Week 52.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the Alzheimer’s Disease Assessment Scale, Cognitive Subscale (ADAS-Cog) score, reported as a mean with standard deviation. The registry describes ADAS as a global rating scale intended to evaluate cognitive and functional aspects associated with disease progression. ADAS-Cog is a subscale made up of short tests assessing possible cognitive impairment.
The listed tasks cover word-finding difficulty, following commands, naming objects and fingers, orientation, word recognition, recall of test instructions, constructions, ideational praxis, spoken language ability, comprehension of spoken language and word recall. Scores range from 0, described as no impairment, to 70, described as serious deficit. In this scale description, a higher score corresponds to greater deficit.
Repeated measurement from baseline to Week 52 allows a comparison of cognitive scores over the study period. Comparing changes between treatment and placebo arms is intended to distinguish change over time in the treatment arm from change over time in the comparator arm. This is a general reason for using a baseline-to-follow-up comparison; it does not establish that a particular observed change is caused by treatment. The registry record gives the endpoint definition and timeframe but does not report the arm means, standard deviations, changes, or between-arm estimate. The numerical result therefore cannot be interpreted from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies ADAS-Cog as the primary outcome and describes its scale, summary measure and assessment timeframe. It does not report numerical ADAS-Cog results. In particular, no arm-specific means or standard deviations at baseline or Week 52, mean changes, between-arm estimate, confidence interval, or p-value are reported in the registry record. Without these results, the direction, magnitude and precision of the primary outcome comparison cannot be assessed.
The listed analysis population is per protocol, defined as participants who received treatment as scheduled and were followed up to week 52. This means the endpoint description does not establish that the reported primary analysis, if any, included everyone randomized. The number analyzed in each arm and the reasons participants might have been excluded are not reported in the registry record. Interpretation of a per protocol comparison generally depends on how adherence and follow-up relate to participant characteristics and outcomes; this is a general methodological consideration, not a finding about this trial.
The record describes a randomized, double-masked, parallel-group design, which sets up a comparison between interferon beta-1a and placebo. Randomization is generally intended to make treatment groups comparable with respect to measured and unmeasured factors, while masking can reduce some forms of influence on treatment delivery or outcome assessment. The registry does not provide procedural details needed to assess how these protections were implemented. The design description alone does not establish the observed treatment effect.
The registry lists nine outcome measures and 24 analyses. Multiple outcomes and analyses can create multiple opportunities to observe apparently notable results by chance. Whether and how this was addressed is not reported in the registry record. Nor are the handling of missing outcome data, the statistical model, or any adjustment for baseline values described. These omissions limit assessment of the analysis, independently of the absent numerical primary outcome results.
The enrollment field lists 42, while the brief summary describes 40 subjects. The record does not explain the difference. These figures should not be treated as interchangeable analysis denominators: enrollment, the population described in a summary, and the participants included in an endpoint analysis can differ. The primary analysis denominator is not reported in the registry record.
Overall, the available record supports a description of the question and design, but not a conclusion about the observed ADAS-Cog comparison. The absence of numerical results is not evidence that the arms were the same, and it does not demonstrate a treatment effect. The appropriate statistical reading is that the primary outcome result and its uncertainty are not reported in the registry record.
9. Statistical Methods Explained
The registry describes the primary outcome as a continuous measure summarized by a mean and standard deviation. It names the ADAS-Cog score and gives baseline and Week 52 as the assessment timeframe. However, the statistical methods used to compare the arms are not reported in the registry record. The following explanations describe general statistical concepts; they should not be read as claims about the analysis actually used in this trial.
What does a mean summarize?
A mean is a measure of the center of a set of scores. For a clinical outcome, it can describe the average score in an arm at a specified assessment or the average change over time. The mean alone does not show how widely individual scores vary, whether the distribution is skewed, or whether a small number of scores strongly influence the result. For that reason, the registry's specification of a standard deviation as the dispersion measure is relevant: the standard deviation describes the spread of scores around the mean, although it does not describe every feature of the distribution.
The record does not report the means or standard deviations for ADAS-Cog. It also does not specify whether the primary comparison used endpoint values, change from baseline, or another model-based contrast. The summary says the study compared neuropsychological performance changes from screening/baseline to Week 52, but this does not identify the exact statistical model or establish how baseline scores were incorporated.
What would a between-arm estimate mean?
A between-arm estimate expresses the contrast between treatment and placebo on the outcome scale. It is more informative for a comparative treatment question than describing change within one arm alone. A change in one group could reflect many influences, including time, measurement, or aspects of study participation; a comparison with the placebo arm helps account for changes also seen in that arm. This is a general interpretation principle, not a numerical result from this trial.
A confidence interval is a range of values compatible with the data and the statistical model at a stated confidence level. It communicates uncertainty around an estimate. A narrow interval indicates greater statistical precision than a wide interval, while an interval that spans values on different sides of no difference may leave the direction of the contrast uncertain. The registry record does not report an ADAS-Cog estimate or confidence interval, so its precision cannot be assessed. No p-value is reported either; statistical significance cannot be inferred from the design or from the safety counts.
Why does the analysis population matter?
The primary outcome is described for a per protocol population: participants who received treatments as scheduled and were followed up to week 52. This population definition focuses on adherence and completion, rather than explicitly stating that all randomized participants were analyzed as assigned. In general, excluding participants after randomization can affect comparability if inclusion is related to prognosis, treatment experience, or outcome. The registry does not report the number analyzed by arm, exclusions, or a separate analysis of all randomized participants.
Missing outcome data can also affect means and treatment comparisons. If participants without Week 52 scores differ systematically from those with observed scores, analysis of available scores alone may give a misleading picture. Statistical approaches can make different assumptions about missing values, so methods and sensitivity analyses matter. The registry record does not report how missing ADAS-Cog values were handled, whether imputation was used, or whether sensitivity analyses were conducted. These are general considerations, not assertions that data were missing or that a particular method was used.
Why do multiple analyses matter?
The record lists nine outcome measures and 24 analyses. When multiple outcomes, time points, or comparisons are examined, the chance of at least one apparently unusual result can increase. A prespecified primary outcome can help focus interpretation, but it does not by itself reveal how secondary analyses were controlled or prioritized. The multiplicity strategy, any hierarchy among outcomes, and any adjustment to significance thresholds are not reported in the registry record.
For a continuous outcome, general analysis choices may include comparison of mean changes, adjustment for baseline scores, or a model that uses repeated measurements. Those methods have different assumptions and may produce different estimates. The registry record does not identify which approach was used, what assumptions were checked, or whether any adjusted or unadjusted analysis was primary. No model diagnostics are reported.
What do the planning illustrations represent?
Planning sample sizes are not observed treatment effects and are not a measure of the trial's observed power. The planning assumptions describe a two-sided significance level of 0.05, equal allocation between arms, a normal approximation, and an effect to detect expressed as a fraction of the observed effect. The registry record does not report the study's own sample-size justification. Any planning illustration based on an observed effect is conditional on that effect estimate and should not be mistaken for evidence that the trial had adequate precision. No recalculated effect estimates or confidence intervals can be interpreted without the outcome summaries, which are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists nine outcome measures and 24 analyses. The primary outcome is identified as ADAS-Cog, but the registry record does not describe a statistical plan for handling multiple outcomes, analyses, or time points. It does not report whether secondary analyses were prespecified, prioritized, or adjusted for multiplicity. In general, examining multiple results can increase the chance of finding an apparently notable result by chance, so selective emphasis on one result should be interpreted cautiously.
Missing-data methods are not reported in the registry record. It does not state whether missing scores occurred, how any missing baseline or Week 52 values were handled, whether imputation was used, or whether sensitivity analyses were performed. These omissions prevent assessment of the assumptions underlying the outcome analysis; they do not establish that missing data were present.
The primary endpoint is described for a per protocol population consisting of participants who received treatment as scheduled and were followed up to week 52. The registry does not report the analysis denominator by arm, exclusions from this population, or a separate intention-to-treat analysis. The enrollment field lists 42, while the brief summary describes 40 subjects; the record does not explain this difference. The count randomized, the population described in the brief summary, and the number analyzed for the endpoint should not be assumed to be the same.
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 |
|---|---|---|---|
| Rebif 22 Mcg | 0 | 23 | 0.0% |
| Placebo | 0 | 19 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Rebif 22 Mcg | 5 of 23 |
| Placebo | 5 of 19 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rebif 22 Mcg | Placebo |
|---|---|---|---|
| High Cholesterol | Investigations | 3 of 23 | 0 of 19 |
| High pseudocholinesterase | Investigations | 2 of 23 | 1 of 19 |
| Articular Pain | Musculoskeletal and connective tissue disorders | 0 of 23 | 2 of 19 |
| Fever | General disorders | 1 of 23 | 0 of 19 |
| High level of alanine transaminase (ALT) and aspartate aminotransferase (AST) | Investigations | 1 of 23 | 0 of 19 |
| High level of aspartate aminotransferase (AST) - alanine transaminase (ALT) | Investigations | 0 of 23 | 1 of 19 |
| High triglycerides | Investigations | 1 of 23 | 0 of 19 |
| High thyroid stimulating hormone | Investigations | 0 of 23 | 1 of 19 |
| Low blood pressure | Vascular disorders | 0 of 23 | 1 of 19 |
| Repolarization ventricular anomaly | Investigations | 1 of 23 | 0 of 19 |
The registry reports serious adverse events as affecting 0 participants in the Rebif 22 Mcg arm, with 23 at risk, and 0 participants in the placebo arm, with 19 at risk. The record lists no serious adverse event terms. Deaths are marked as null, which means death figures are not reported in the registry record; null should not be read as zero.
For other adverse events, the registry reports 5 affected participants among 23 at risk in the Rebif 22 Mcg arm and 5 among 19 at risk in the placebo arm. These are counts of affected participants as recorded, not a description of event type, severity, timing, or duration. The record does not provide details of the events or state whether participants could contribute more than one event.
These counts are descriptive. They do not establish that the arms had equivalent safety profiles or that a difference is present. Small safety counts can leave substantial uncertainty, and interpretation depends on the event definitions, follow-up, and completeness of reporting. The registry record does not provide those details or report a statistical comparison of adverse events. The safety figures should therefore be read as the recorded counts, not as a definitive comparative estimate.
12. What the Result Does, and Does Not, Mean
The registry record establishes the trial's broad question: whether the change in cognitive performance measured by ADAS-Cog from baseline to Week 52 differed between a group assigned interferon beta-1a and a group assigned placebo. It also identifies the study as randomized, double-masked, parallel-group and phase II. These features describe the intended comparison, not its outcome.
The record does not report numerical ADAS-Cog results. There is no arm-specific mean, standard deviation, change, between-arm estimate, confidence interval, or p-value from which to judge the size, direction, or precision of the primary comparison. Accordingly, the record does not establish whether the groups differed on this outcome. Missing numerical results cannot be interpreted as a finding of no difference, nor can the stated study objective be treated as evidence of an effect.
The endpoint is a cognitive scale with a stated range from 0, no impairment, to 70, serious deficit. A comparison on this scale would need to be interpreted in light of the observed values and their uncertainty. The registry describes the measurement but does not provide the results needed to connect score changes to the trial's comparative question. Other outcome measures are listed, but their numerical results are not included in the record.
The safety record reports 0 participants with serious adverse events in each arm, alongside the reported at-risk counts, and records 5 participants affected by other adverse events in each arm. The death entries are not reported. These figures describe recorded events; they do not by themselves establish comparative safety or rule out events not captured in the record.
More broadly, the findings cannot be generalized beyond what the registry documents. The number analyzed for the primary endpoint, missing-data handling, multiplicity approach, and detailed analysis methods are not reported in the registry record. These gaps, along with the difference between the enrollment field and the narrative study count, limit a full assessment. The record supports a description of study design and selected safety counts, but not a conclusion about the ADAS-Cog treatment comparison.
13. Why This Trial Matters Statistically
This trial illustrates why a study's design and its numerical results answer different questions. Randomization, double masking and a parallel-group comparison describe how the investigators intended to compare interferon beta-1a with placebo. They do not reveal the observed difference in ADAS-Cog or how precisely that difference was estimated. Because the registry record does not report numerical primary outcome results, the central comparative finding cannot be evaluated from this record.
The endpoint also highlights the importance of specifying the population being analyzed. ADAS-Cog is described for a per protocol population, defined by scheduled treatment and follow-up through Week 52. That is not, by itself, a complete account of who was analyzed or how participants not meeting the definition were handled. The enrollment field and narrative study count also differ, with no explanation in the registry record. Clear denominators and transparent participant flow are important for understanding what a reported mean represents.
The listing of nine outcome measures and 24 analyses raises a general statistical issue: multiplicity. Readers need to know which outcome was primary, how analyses were selected, and whether any multiplicity strategy was used. The record identifies the primary outcome but does not report such a strategy. This matters when interpreting a collection of outcome results, even when a primary endpoint has been named.
Finally, the record separates a limited safety description from a full comparative safety analysis. The serious and other adverse-event counts are useful descriptive information, but the event details, deaths, and analysis methods are not fully reported. Together, these features make the trial statistically instructive: design labels, endpoint definitions, analysis populations, uncertainty estimates, and complete outcome reporting are all needed for a sound interpretation.
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 central limitation for interpreting the primary outcome is that numerical ADAS-Cog results are not reported in the registry record. Without arm-specific summaries and a comparative estimate with its uncertainty, the direction and precision of the primary comparison cannot be evaluated.
The record lists enrollment as 42, while the brief summary describes a study conducted in 40 subjects. It does not explain the difference. The number randomized, the number meeting the summary description, and the number included in the per protocol endpoint analysis are not reported separately. The registry also does not provide participant flow, reasons for withdrawal or exclusion, or the number with Week 52 assessments.
Important analysis details are not reported: the statistical model, handling of baseline values, missing-data methods, multiplicity strategy, and sensitivity analyses. The record defines the per protocol population but does not state whether an analysis of all randomized participants was also performed. These gaps limit assessment of the assumptions and robustness of any outcome analysis.
The safety information is also limited. Counts are given for serious and other adverse events, but event descriptions and detailed reporting methods are not available; deaths are not reported. The registry does not provide a sample-size justification for the trial, and does not explain the randomization or masking procedures. These limitations concern the information in the registry record and do not establish that the study itself lacked procedures or analyses not recorded there.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Pilot Trial of Interferon Beta-1a in Alzheimer's Disease — NCT01075763.
- Registry record last updated 2014-02-13; status last verified 2014-01.
- Results first posted 2012-04-04.
- 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 record describes a completed, randomized, double-masked, parallel-group phase II pilot study of interferon beta-1a versus placebo in Alzheimer's disease. The brief summary describes a 52-week multicentric study; treatment was subcutaneous Rebif® 22 microgram three times per week. The primary outcome was mean ADAS-Cog score at baseline and Week 52 in a per protocol population.
The enrollment field lists 42, while the brief summary describes 40 subjects. Numerical results for the primary outcome and details of the statistical analysis are not reported in the registry record. Serious adverse events affected 0 participants in each arm; other adverse events affected 5 participants in each arm. Deaths are not reported.