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 Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS) (NCT01786603), a randomized phase 2 study. The primary outcome is ALS Functional Rating Scale-Revised (ALSFRS-R).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01786603 |
| Phase | Phase 2 |
| Condition | Amyotrophic Lateral Sclerosis (ALS) |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 80 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Richard Barohn, MD |
| Results posted | Yes |
2. Clinical Question
Population
People with amyotrophic lateral sclerosis (ALS). The registry describes ALS as a disorder involving weakening motor strength and lung function, and identifies this as a phase 2 study.
Intervention
Rasagiline, administered orally once daily for 12 months. The arm description uses both 1mg and 2mg wording; the registry record does not clarify that wording further.
Comparator
Placebo, described as an inactive ingredient and administered once daily for 12 months.
Primary question
How did the ALS Functional Rating Scale-Revised (ALSFRS-R) score change from baseline to Month 12 in each study group? The registry posts group means and confidence intervals, but does not report a primary between-group estimate or test.
The study aimed to examine whether rasagiline was safe and whether it slowed disease progression in people with ALS. Rasagiline was described as investigational for ALS, and the registry notes that it is approved for treatment of Parkinson's disease. The trial used randomized allocation, triple masking, and a parallel-group model. Registry enrollment was 80.
The central interpretive distinction is between describing change within each group and estimating a treatment contrast. The posted primary results describe average ALSFRS-R change from baseline in the rasagiline and placebo groups. They do not, by themselves, quantify how much the average change differed between the groups. That primary comparative estimate, its uncertainty, and a corresponding test are not reported in the registry record.
3. Trial Design
This was a phase 2 randomized, triple-masked, parallel-group study of rasagiline and placebo in ALS. The registry lists enrollment of 80 and marks the study completed. The listed study dates are 2013-11-21 for the start and 2016-07-27 for primary completion. These dates describe the registry record; they do not establish the duration of follow-up for every participant.
The registry describes rasagiline as an oral once-daily treatment for 12 months and placebo as an inactive ingredient given once daily for 12 months. The rasagiline arm description states “Rasagiline 1mg administered orally as a 2mg single dose once daily for 12 months.” The placebo description also combines 1mg and 2mg wording. The registry record does not clarify these descriptions, so they should not be silently reconciled into a different dose description.
The posted primary results give a group size of 60 for rasagiline and 20 for placebo. The reason for the unequal group sizes, and whether they reflect the original allocation plan or the analysis population, is not reported in the registry record. The registry identifies the study as randomized, but does not report the sequence-generation method or allocation-concealment procedures. It labels masking as triple without specifying which roles were masked.
The primary outcome was change in ALSFRS-R score from baseline to Month 12. Listed secondary outcomes include vital capacity, quality of life, adverse events, survival status, apoptosis markers, and oxidative stress. Quantitative registry results are posted for survival status, apoptosis markers, and oxidative stress. Details of the planned statistical analysis, analysis populations, handling of missing measurements, and any interim analyses are not reported in the registry record.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | Rasagiline | Placebo |
|---|---|---|
| STARTED | 60 | 20 |
| COMPLETED | 42 | 8 |
| NOT COMPLETED | 18 | 12 |
Reasons for not completing this period:
| Reason | Rasagiline | Placebo |
|---|---|---|
| Death | 5 | 1 |
| Adverse Event | 6 | 2 |
| Physician decision to withdraw | 6 | 7 |
| Lost to Follow-up | 1 | 2 |
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 | Rasagiline | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 60 | 20 | 80 | |
| Age, Continuous | years | 58.4 (SD 10.2) | 57.5 (SD 8.5) | 57.95 (SD 9.35) |
| Sex: Female, Male: Female | Participants | 20 | 7 | 27 |
| Sex: Female, Male: Male | Participants | 40 | 13 | 53 |
6. Primary Endpoint
The registry lists the primary outcome as ALS Functional Rating Scale-Revised (ALSFRS-R), measured over ALS Functional Rating Scale-Revised (ALSFRS-R) Difference from Baseline to Month 12.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint is the change in ALS Functional Rating Scale-Revised (ALSFRS-R) score from baseline to Month 12. The registry describes the ALSFRS-R as an ordinal rating scale covering 12 functional activities. Each activity is scored between 0-4, and the total score ranges from 48, representing normal function, to 0, representing no function. The endpoint therefore records a change in a rating of functional activities over the stated period.
A functional scale can provide a common outcome measure across study participants, allowing the results to describe average change in function over time. The registry reports the endpoint as a mean with a 95% confidence interval for each group. Because the scale is ordinal, the mean is a group-level summary; it does not show the pattern of individual participant scores or changes.
The posted values are changes within each group, not a direct estimate of the difference in change between rasagiline and placebo. A comparison of treatment groups is needed to estimate a treatment contrast. That contrast and its uncertainty are not reported for the primary endpoint in the registry record. The endpoint description also does not report how deaths or missing Month 12 scores were handled in calculating the posted means.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted primary results show a mean ALSFRS-R change from baseline to Month 12 of -1.0 in the rasagiline group, with a 95% confidence interval from -1.22 to -0.77. In the placebo group, the mean change was -1.26, with a 95% confidence interval from -1.64 to -0.87. These are separate estimates of average change within each group.
The confidence intervals convey uncertainty around those group means under the analysis used to produce them. They do not give the probability that the true mean lies within a particular interval, and they do not replace a direct comparison between groups. The registry record does not report a primary between-group estimate, confidence interval for that estimate, or p-value. It is therefore not possible from these posted primary results to quantify the precision of the treatment contrast or to assess a reported primary hypothesis test.
The negative mean changes indicate that the average recorded score at Month 12 was lower than baseline in both groups. The scale description associates higher scores with more function, but the group means alone do not reveal how individual participants changed, how changes were distributed, or whether the apparent difference between the group means is compatible with chance variation. Those questions require the comparative analysis and its methods, which are not reported for the primary endpoint.
Registry enrollment is 80, while the primary outcome results list 60 participants in the rasagiline group and 20 in the placebo group. The record does not explain whether these are randomized, treated, or analyzed participants, or whether any participants lacked an endpoint measurement. The group counts should not be taken as evidence that all participants enrolled contributed complete Month 12 data.
Secondary results include some unadjusted comparisons recalculated from posted summary statistics. Such calculations are not a substitute for the sponsor's analysis, and the registry lists no reported analyses for these outcomes. They also involve outcomes beyond the primary measure. Their estimates should be read as exploratory descriptions, especially because the record does not state how multiplicity was addressed. A nominal p-value for a secondary outcome does not establish a confirmatory result, nor does it resolve the missing primary comparative analysis.
Overall, the record documents the trial design and provides within-group primary outcome summaries. It does not provide the principal numerical comparison needed to judge the primary endpoint as a randomized group contrast. The posted information can describe changes in the two groups, but supports only limited inference about a treatment effect.
9. Statistical Methods Explained
What does a group mean describe?
A mean summarizes the observed values in a group by expressing their average. For a change endpoint, it summarizes the average change among the observations included in that calculation. It does not say that every participant changed by the mean amount, and it can conceal variation in individual outcomes. The ALSFRS-R is described as an ordinal scale, so reporting a mean is one way of summarizing group-level results, not a complete description of the underlying score distribution.
What does a confidence interval add?
A confidence interval gives a range of values compatible with the estimate under the method's assumptions. A narrower interval indicates greater precision than a wider interval, all else equal. It is not a range containing most individual participant outcomes, and it is not a probability statement about a fixed true value after the interval has been calculated. For the primary outcome, the registry gives a 95% confidence interval for each group mean. Those intervals express uncertainty about the group means, not directly about the difference between groups.
Why is the treatment contrast important?
In a randomized comparison, the treatment question concerns how outcomes differ between assigned groups. A direct between-group estimate would quantify that contrast and report its uncertainty. Separate within-group estimates do not provide that contrast by themselves. Even when the group means appear different, a reader needs the estimated contrast, its confidence interval, and the analysis details to assess precision and interpret the comparison. The registry record does not report those primary comparative results.
What do recalculated secondary comparisons represent?
Some secondary comparisons are simple unadjusted recalculations from posted summary statistics. For continuous outcomes, a mean difference describes the difference between group means; for a binary outcome, a risk difference describes the difference between the proportions represented by the posted counts. These calculations do not account for covariates or other design features unless those are explicitly included, and the registry does not report a sponsor analysis for these comparisons. The record marks no discrepancy between its posted results and these recalculations. Nevertheless, a recalculation should not be mistaken for a reported sponsor analysis or a prespecified analysis plan.
Why can over-dispersion matter?
General statistical explanation: over-dispersion occurs when observed variability is greater than a model assumes. If a method assumes less variability than is present, its uncertainty estimates can be too small and its intervals too narrow. If variability is greater, a model that accommodates it can produce more realistic uncertainty. This is a general consideration, not a claim that over-dispersion occurred in this trial. The registry record does not report model diagnostics or an analysis method for the primary endpoint.
What does a p-value say?
General statistical explanation: a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the model assumptions were true. It does not measure the size or importance of an effect, and it is not the probability that the null hypothesis is true. A p-value also does not correct for examining multiple outcomes. The secondary recalculations are unadjusted; the registry record does not report a multiplicity procedure. No primary p-value is reported.
How should planning illustrations be read?
The secondary planning illustrations use the observed effect as a starting point, with stated fractions of that effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They estimate participants per arm for stated power targets under those assumptions. They are not the trial's original sample-size justification, and they are not observed power. The sample-size assumptions say that these illustrations are not based on the trial's own design. The registry record does not report the original sample-size justification or its assumptions.
Planning calculations based on an observed effect are especially sensitive to the stability of that estimate. A noisy observed effect can produce planning values that do not represent a reliable expectation for a future study. Considering a fraction of the observed effect is one way to examine sensitivity to a smaller target effect; it does not establish which effect is clinically important. The registry record does not report a clinically important threshold for these outcomes.
What information is needed to interpret an analysis?
Interpretation depends on more than an estimate and its uncertainty. The analysis population, missing-data rules, handling of deaths, and statistical model can affect what the result represents. For a repeated or longitudinal outcome, the chosen analysis can also determine how measurements at different times contribute. These details are not reported for the primary endpoint in the registry record. That absence limits assessment of whether the posted summaries reflect all randomized participants, participants with observed measurements, or another defined population.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report whether the trial used a multiplicity adjustment or a hierarchy among endpoints. It lists a primary endpoint and six secondary outcomes, including several distinct clinical and biological measures. Examining multiple outcomes creates multiple opportunities to observe a nominally unusual result. Without a stated strategy for controlling or interpreting those opportunities, unadjusted secondary p-values should be treated as exploratory rather than as independent confirmatory evidence.
The record lists zero reported analyses. In particular, it does not report the primary between-group estimate or test, a formal analysis plan, or the method used to produce the primary group summaries. The absence of a reported analysis is not evidence that no analysis was performed; it means the registry record does not document one for interpretation.
Missing-data handling is not reported in the registry record. It does not state how missing Month 12 scores were treated, whether a statistical method used incomplete repeated measurements, or whether any values were imputed. It also does not describe how death was handled in the primary functional outcome analysis. The posted group sizes therefore cannot establish completeness of follow-up or show which participants contributed to each endpoint.
The analysis populations are not defined in the registry record. It does not state whether primary results followed an intention-to-treat approach, included only participants who received treatment, or used another population. The outcome counts and the registry's enrollment figure should not be used to infer the analysis set. These omissions matter because exclusions, missing outcomes, and the handling of death can affect both the interpretation of an estimate and its generalizability to the randomized groups.
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 |
|---|---|---|---|
| Rasagiline | 0 | 60 | 0.0% |
| Placebo | 0 | 20 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Rasagiline | 5 of 60 |
| Placebo | 1 of 20 |
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 |
|---|---|
| Rasagiline | 28 of 60 |
| Placebo | 15 of 20 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Rasagiline | Placebo |
|---|---|---|---|
| Gastrointestinal | Gastrointestinal disorders | 22 of 60 | 12 of 20 |
| Musculoskeletal | Musculoskeletal and connective tissue disorders | 15 of 60 | 9 of 20 |
| Nervous System | Nervous system disorders | 16 of 60 | 6 of 20 |
| Respiratory | Respiratory, thoracic and mediastinal disorders | 15 of 60 | 7 of 20 |
| Psychiatric | Psychiatric disorders | 11 of 60 | 6 of 20 |
| General Disorders | General disorders | 12 of 60 | 3 of 20 |
| Vascular | Vascular disorders | 7 of 60 | 8 of 20 |
| Infections | Infections and infestations | 11 of 60 | 3 of 20 |
| Injury, Poisoning, Procedural Complications | Injury, poisoning and procedural complications | 11 of 60 | 3 of 20 |
| Metabolism and Nutrition | Metabolism and nutrition disorders | 10 of 60 | 3 of 20 |
The registry reports zero serious adverse events among 60 participants at risk in the rasagiline group and zero among 20 at risk in the placebo group. It reports other adverse events in 28 participants at risk of 60 in the rasagiline group and 15 at risk of 20 in the placebo group. The record lists 5 deaths in the rasagiline group and 1 in the placebo group.
These are counts as recorded, not estimates of causal effects. The registry does not provide serious adverse event terms, and zero recorded serious events does not establish that no clinically important safety issue occurred outside the recorded categories or reporting period. The record does not explain whether deaths overlap with adverse-event counts, how events were attributed, or the exposure time contributing to the counts. It also does not report a comparative safety analysis. The figures should therefore be read as descriptive registry counts, not as proof of equivalence or as a basis for concluding that either group had greater treatment-related risk.
12. What the Result Does, and Does Not, Mean
The posted results establish that the registry reports average ALSFRS-R changes from baseline to Month 12 for both groups, with 95% confidence intervals around those means. They also document several secondary outcome summaries and descriptive adverse-event counts. This is useful information about what was recorded and the precision reported for the group means.
Those results do not establish the size or precision of a primary treatment contrast. A randomized design makes a between-group comparison central to the treatment question, but the registry record does not report that primary estimate or a test. The within-group changes cannot substitute for it. Nor can the secondary recalculations establish the primary result, particularly when their analyses are unadjusted and the multiplicity approach is not reported.
The confidence intervals around the primary group means describe uncertainty in those means, not the range of possible individual changes. They also do not answer whether any difference between groups is compatible with chance variation. The registry does not report a clinically important threshold for interpreting score changes, so the posted mean changes alone cannot determine whether their magnitude would be meaningful to patients or researchers.
Missing-data methods, analysis populations, and the handling of deaths are not reported. Consequently, the record does not establish how completely the results represent participants assigned to each group. The adverse-event figures are also descriptive; they do not prove that an event was caused by treatment or that the groups had equivalent safety.
In short, these registry results support a description of reported group-level outcomes and their stated uncertainty. They do not, on their own, provide a complete inferential answer to the primary comparative question or establish a treatment benefit, lack of benefit, or safety equivalence.
13. Why This Trial Matters Statistically
This trial is statistically informative because it illustrates the difference between a group summary and a randomized comparison. The primary outcome is reported as a mean change with a confidence interval in each group. Those summaries help describe the observed data, but the missing between-group estimate leaves the main comparative question without a directly reported numerical answer.
The distinction is important in clinical research. A reader may be tempted to compare two group means informally, but the uncertainty of their difference is not given by either confidence interval alone. A direct estimate and its uncertainty are needed to assess the comparative result. Clear reporting of the analysis population, model, and missing-data approach would further help readers understand what that estimate represents.
The trial also has multiple secondary outcomes spanning functional, respiratory, quality-of-life, survival, safety, and biological measures. This breadth can provide a wider view of the study, but it raises the importance of stating how outcomes were prioritized and how multiplicity was addressed. Without that information, secondary findings are best treated as descriptive or hypothesis-generating rather than as substitutes for a primary analysis.
Finally, the record distinguishes planned sample-size illustrations from the trial's original design rationale. Calculations based on observed effects can show how planning assumptions influence future study sizes, but they do not describe the power achieved by this completed trial. The original sample-size justification is not reported. Together, these issues make the record useful for learning how to interpret estimates, intervals, and exploratory comparisons while also showing why complete statistical reporting matters.
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.
Several limitations specific to this record constrain interpretation. First, the primary endpoint is posted as a mean and confidence interval within each group, but no primary between-group estimate or test is reported. That omission prevents direct assessment of the central randomized comparison. The record also does not describe the statistical model or clarify whether the confidence intervals account for features such as repeated measurements.
Second, the reported group sizes are unequal: 60 for rasagiline and 20 for placebo, while registry enrollment is 80. The registry does not explain the reason for the imbalance or define the population represented by each outcome count. It also does not report missing-data handling, analysis-population definitions, or the treatment of deaths in the functional endpoint. These uncertainties limit assessment of selection, attrition, and the meaning of the group summaries.
Third, masking is described as triple, but the masked roles and practical procedures are not specified. The rasagiline and placebo arm descriptions contain both 1mg and 2mg wording, which the record does not clarify. These are reporting ambiguities; the record does not permit a more precise reconstruction.
Finally, the secondary comparisons are unadjusted recalculations, and the registry lists no reported analyses or multiplicity strategy. Secondary outcomes measure different constructs and cannot be treated as replacements for the primary comparison. The original sample-size justification, clinical importance thresholds, and detailed safety analysis are not reported in the registry record. These limitations do not negate the posted descriptive results, but they restrict how strongly they can support comparative conclusions.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS) — NCT01786603.
- Registry record last updated 2020-01-27; status last verified 2020-01.
- Results first posted 2020-01-27.
- 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 NCT01786603, “Rasagiline in Subjects With Amyotrophic Lateral Sclerosis (ALS),” as a completed phase 2 randomized, triple-masked, parallel-group study. It lists enrollment of 80 and compares rasagiline with placebo over a stated treatment period of 12 months.
The primary outcome is ALSFRS-R change from baseline to Month 12. The record reports group means and 95% confidence intervals, but not a primary between-group estimate or test. It also lists six secondary outcomes and posts quantitative results for survival status, apoptosis markers, and oxidative stress, alongside descriptive adverse-event counts.
Analysis populations, missing-data handling, multiplicity procedures, the primary statistical method, and the original sample-size justification are not reported in the registry record. The posted results therefore support descriptive reading of the recorded outcomes, while leaving important parts of the primary comparative analysis undocumented.