A Multi-Center Controlled Screening Trial of Safety and Efficacy of Lithium Carbonate in Subjects With Amyotrophic Lateral Sclerosis (ALS): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Multi-Center Controlled Screening Trial of Safety and Efficacy of Lithium Carbonate in Subjects With Amyotrophic Lateral Sclerosis (ALS) (NCT00790582), a na phase 2 study. The primary outcome is Change in Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised).

2. Clinical Question

The study was intended to screen lithium carbonate for safety and for a possible effect on disease progression in people with ALS. Those aims are not equivalent to a controlled estimate of treatment effect. Without a concurrent comparison group, changes over time in the treated group cannot by themselves distinguish a treatment effect from the course of the condition, variation in measurement, or other influences.

The primary endpoint is a functional measure. The registry describes a score based on 12 questions about activities involving the mouth area, arms, legs, and breathing. The planned assessment schedule includes baseline and follow-up through Month 13. However, a schedule and endpoint description do not establish what change was observed. The posted record contains no primary-outcome analysis, so the treatment-versus-comparator question cannot be answered from the recorded results.

3. Trial Design

This is a completed Phase II trial listed as a single-group study. The registry reports enrollment of 109 and names lithium carbonate as the intervention. The brief summary says there is no placebo and that all patients would take lithium carbonate. Masking is listed as none, and allocation is listed as NA. These design features mean the registered trial was not a randomized, masked comparison of lithium carbonate with placebo.

The registry gives a start date of 2008-05 and a primary completion date of 2010-03. These dates describe the record’s trial timeline; they do not indicate how many participants completed follow-up or contributed data to the primary endpoint. Completion status is listed as completed, but outcome analyses are not posted in the registry record.

The record lists historical controls in its adverse-event information. Historical controls are observations from a separate prior group, rather than a concurrently allocated group in the same trial. The registry itself cautions that the arms are not a like-for-like control comparison. Differences in participant selection, observation periods, or how events were recorded could affect comparisons; details needed to assess those issues are not reported in the registry record. The historical-control counts therefore should not be read as if they came from a randomized control arm.

The primary endpoint is described as change in the monthly rate of decline in the ALSFRS-R. The listed timeframe includes baseline and repeated follow-up assessments through Month 13. Vital capacity is named as a secondary outcome, and the record reports 2 outcome measures. It does not report numerical results for either outcome. The record also does not report the protocol’s sample-size justification or an interim-analysis plan. A planning illustration based on an observed effect, where available, would not itself document the design rationale or constitute an observed trial result.

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.

Before assignment: This was an open label single-arm Phase II screening trail. All enrolled subjects (n=109) were treated. Their results were compared with placebo subjects from an historical database of ALS placebo patients from recent studies (n=249). Thus the number enrolled (n=109) does not equal the total number of subjects (n=358). Enrolled subjects started lithium carbonate at 150 mg twice daily. If subjects did not tolerate a dose it was tapered by 150 mg increments to the maximum tolerated dosage.

Overall Study

Reasons for not completing this period:

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 Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised), measured over Baseline, Month 1,3,4.5,6,7.5,9,10.5,12,13.

The registered primary endpoint is “Change in Monthly Rate of Decline in ALSFRS-R (Amyotrophic Lateral Sclerosis Functional Rating Score - Revised),” with units of points per month. The record describes the ALSFRS-R as a 12-question questionnaire about a person’s ability to complete daily activities. It includes questions about the mouth area, arms, legs, and breathing. Each question is scored from 0, described as worst, to 4, described as normal function; the record gives 48 as the maximum possible score and 0 as the minimum.

In general, a repeated functional measure can be used to track how a person’s reported abilities change over time. Describing a rate of decline expresses change relative to time, rather than only reporting a score at one visit. This can be useful when the scientific question concerns progression, but interpretation depends on the prespecified definition of the rate and how repeated measurements are analyzed. Those analysis details are not reported in the registry record.

The planned assessments are listed at baseline and Month 1, 3, 4.5, 6, 7.5, 9, 10.5, 12, and 13. The endpoint’s stated dispersion is a 95% confidence interval. In general, a confidence interval communicates uncertainty around an estimated quantity; it is not itself the estimated change. No estimate or confidence interval for this primary outcome is reported in the registry record. The endpoint description and assessment schedule therefore clarify what was intended to be measured, but they do not show the observed trajectory or its precision.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the outcome type as continuous and describes the primary measure using a mean and a 95% confidence interval. These terms indicate how a numerical functional outcome was intended to be summarized. The record does not provide the calculated mean change or confidence interval, nor does it describe the exact statistical model used to estimate the monthly rate. Consequently, the endpoint’s statistical description can be explained, but the trial’s observed primary result cannot be reconstructed from the registered information.

What does a mean describe?

In general, a mean is a measure of the center of numerical observations. For a continuous outcome such as a functional score or a rate of score change, it can summarize the group’s average value. A mean does not show how much individual observations vary, whether the distribution is symmetric, or whether every participant followed a similar trajectory. Those features require additional data or summaries, which are not reported in the registry record.

The endpoint is expressed as a monthly rate of decline. A rate links change in the measure to time, and the planned repeated assessments can provide information about the pattern of scores over follow-up. However, the registry does not specify how measurements at the listed visits were combined, whether the rate was estimated for each participant or across the group, or how incomplete follow-up was handled. Those choices can affect the estimate and its interpretation. They are not reported in the registry record, so no particular method should be assumed.

How should a confidence interval be read?

In general, a confidence interval gives a range of values compatible with an estimate under the analysis assumptions. It communicates statistical uncertainty, not the range of individual participant outcomes. A narrower interval indicates greater precision for that estimate under the method used; a wider interval indicates less precision. The registry names a 95% confidence interval as the endpoint’s dispersion, but does not post the interval or describe its construction. It is therefore not possible to judge the precision of the primary estimate from the registry record.

Confidence intervals also do not resolve design limitations. Even a precise estimate of change within a single group would not, on its own, provide a controlled estimate of the intervention’s effect. The trial is listed as single-group, with no placebo and no masking. In general, an intervention comparison is stronger when the comparison group is observed over the same period under a design that supports causal interpretation. The historical controls listed for safety are not identified as a concurrent randomized group, and the registry cautions against treating the groups as like-for-like.

What does the study design allow?

The record describes a Phase II screening study intended to examine safety and whether lithium carbonate might slow progression. A screening objective can motivate evaluation of outcomes and inform further research, but it does not change what the design can establish. Without a concurrent comparator for the primary functional endpoint, observed change among participants taking lithium carbonate cannot be attributed solely to the intervention. The record does not report a protocol, detailed statistical analysis plan, or model assumptions that would further define the analysis.

The registry lists allocation as NA, masking as none, and the model as single-group. These are design descriptors, not results. The enrollment figure is not the same as the number with complete follow-up or the number included in an outcome analysis. The registry record does not report those analysis counts or how missing measurements were treated. It also does not report whether analyses were based on all enrolled participants, participants with available measurements, or another defined population.

How do planning illustrations differ from trial results?

General sample-size calculations estimate how many participants may be needed under stated assumptions to detect a specified effect with a chosen statistical procedure. The planning assumptions recorded for this trial include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. For time-to-event calculations, the stated quantity is total events; for other calculations, it is participants per arm.

These assumptions describe a planning illustration, not the design of the completed single-group trial. The record explicitly characterizes the illustration as computed from the observed effect rather than from the trial’s own design. Such values should not be called observed power, and they do not demonstrate that the effect occurred or that a future study would reproduce it. The primary endpoint estimate needed to evaluate an effect is not reported in the registry record. The trial’s own sample-size justification is also not reported in the registry record.

Why do outcome and safety summaries need context?

For continuous outcomes, the mean and its uncertainty are only part of the evidence; the design, analysis population, missing-data approach, and measurement schedule also matter. For adverse events, counts need a clear definition of who was at risk, how long they were observed, and how events were classified. In general, differences between a trial cohort and historical controls may reflect differences in the groups or their observation and recording, as well as any true difference in event experience. The registry does not provide enough detail to separate these explanations.

Statistical methods should therefore be interpreted alongside the available outcome information and study design. Here, the registered methods identify a continuous primary endpoint and a stated confidence-interval format, but no primary analysis is posted. No statistical significance test, adjusted estimate, or treatment-effect conclusion can be extracted from the record. The method labels define what was planned or recorded; they do not substitute for the missing numerical results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 2 outcome measures, with the ALSFRS-R monthly rate of decline as the primary outcome and Vital Capacity as a secondary outcome. When a study evaluates more than one outcome, or several analyses of an outcome, multiplicity can matter: conducting multiple statistical tests can increase the chance of at least one apparently positive finding by chance. In general, a statistical plan may specify a primary comparison, a testing hierarchy, or an adjustment. The registry record does not report a multiplicity strategy or the results of tests for these outcomes.

The record lists 0 analyses. It therefore does not provide a posted primary-outcome estimate or secondary-outcome analysis to interpret. The analysis populations, participant flow at follow-up visits, and the number contributing to each outcome are not reported in the registry record. Enrollment of 109 should not be taken to mean that every enrolled participant contributed data at each planned assessment.

Missing data can affect estimates when outcome measurements are unavailable. In general, the implications depend on why data are missing and on the method used to address them. The registry record does not report the extent or pattern of missing measurements, a missing-data method, or sensitivity analyses. It also does not report an analysis population definition, such as whether an analysis was planned for all enrolled participants or only those with particular observations.

The registry record does not report an interim-analysis plan or the trial’s statistical analysis plan. These omissions prevent assessment of how outcomes, repeated observations, missing measurements, or multiple analyses were handled. They do not establish that such methods were absent from other trial documents; they mean those details are not reported in the registry record.

11. 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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: respiratory (22.9%), other (18.3%), gastrointestinal (15.6%).

The registry lists serious adverse-event counts for the lithium carbonate group as 62 affected among 109 at risk. For historical controls, it lists 91 affected among 249 at risk. The record also lists other adverse-event counts: 99 affected among 109 at risk in the lithium carbonate group and 175 affected among 249 at risk in historical controls. Death counts are listed as 14 and 44, respectively.

These are descriptive counts. The registry identifies the historical controls as not a like-for-like comparison, and the study itself is single-group rather than randomized. The counts should not be interpreted as a causal comparison or as proof that lithium carbonate caused or prevented an event. The registry does not report event definitions, observation periods, detailed ascertainment procedures, or an adjusted comparative analysis. Without that context, the counts do not by themselves establish comparative safety.

The registry lists the leading serious-event terms as Respiratory at 22.9%, Other at 18.3%, and Gastrointestinal at 15.6%. The denominator and calculation used for those percentages are not reported in the registry record. Event categories and percentages should therefore be read as registry summaries, not as fully specified incidence estimates.

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

The record documents a completed Phase II screening study of lithium carbonate in people with ALS, with enrollment of 109 and a planned functional primary endpoint. It also records adverse-event counts for the lithium carbonate group and historical controls. These registry entries describe the study’s registration and posted safety information, but they do not constitute a reported estimate of change in the primary functional outcome.

The primary endpoint was intended to measure change in the monthly rate of decline on the ALSFRS-R. The record gives the scale description, planned assessment schedule, and intended confidence-interval format. It does not report the endpoint estimate or interval. As a result, the posted information does not establish the direction, magnitude, or precision of functional change during follow-up. The missing result should not be interpreted as showing no change or no effect.

The design also constrains conclusions. This was a single-group, unmasked study without a placebo. Changes observed over time in a treated group would not alone identify what would have happened without the intervention. Historical-control safety figures are not a substitute for a concurrent randomized comparison, and the registry explicitly cautions that they are not like-for-like.

The safety counts can be read as the number affected among the number listed at risk in each group. They do not, without additional information, establish a causal relationship or a reliable comparative risk. Event definitions, follow-up periods, and comparative analyses are not reported in the registry record. Nor are primary or secondary outcome analyses posted.

In general, a screening study may identify questions for further investigation, but the available record does not show whether this study met a particular efficacy or safety criterion. The registry entry supports description of the design, intended endpoint, and recorded counts. It does not support a conclusion about treatment benefit, lack of benefit, or comparative safety.

13. Why This Trial Matters Statistically

This trial illustrates why a study’s objective, design, and posted results must be considered separately. The registry describes an aim to assess safety and whether lithium carbonate might slow disease progression, and it specifies a repeated functional endpoint. Yet the study is listed as single-group, with no placebo and no masking. A clear endpoint does not remove the limitations of a design without a concurrent comparison for estimating an intervention effect.

The endpoint is a rate of change in a functional score rather than a single score at one time. In general, rates derived from repeated measures can be informative about progression, but their interpretation depends on the observation schedule, the model or calculation used, and how incomplete measurements are handled. The registry provides the planned visit times and endpoint units, but not the primary analysis or those methodological details. This distinction matters because a measure’s name and schedule are not evidence of an observed result.

The safety entries also demonstrate the need to distinguish descriptive counts from comparative evidence. The record lists historical controls, while warning that they are not a like-for-like comparison. A historical group may provide context, but differences in participant characteristics, observation, or event recording can complicate direct comparisons. The posted counts alone cannot isolate an intervention-related difference.

Finally, the record lists no analyses, and it does not report missing-data methods, analysis populations, or multiplicity procedures. Those details are essential for understanding how planned endpoints became statistical estimates and how uncertainty should be interpreted. The case therefore highlights a general lesson in biostatistics: registration details clarify what a trial set out to do, while conclusions require interpretable results and a design capable of supporting the intended comparison.

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 primary limitation for interpreting this record is the absence of posted outcome analyses. Although the registry identifies the primary endpoint and its planned assessment schedule, it does not report an estimate or confidence interval. Vital Capacity is listed as a secondary outcome, but no result is posted for it either. The record lists 0 analyses, so the outcome information is insufficient to assess the observed functional trajectory or its uncertainty.

The single-group design, lack of masking, and absence of a placebo limit causal interpretation. The registry lists historical controls in the safety information but cautions that the groups are not like-for-like. Those historical observations cannot be treated as a randomized concurrent comparison. The record does not report the details needed to evaluate comparability, event ascertainment, or differences in follow-up.

The registry does not report how many participants contributed outcome data at each visit, how many completed follow-up, or how missing measurements were handled. It also does not report an analysis-population definition, the statistical model for the repeated endpoint, or a multiplicity strategy. These gaps limit assessment of the planned methods and the representativeness and precision of any estimates that might have been calculated outside the posted record.

The record reports an enrollment figure, but enrollment alone does not establish the number analyzed for any endpoint. It does not report the trial’s own sample-size justification or an interim-analysis plan. The planning assumptions recorded for sample-size illustrations should not be treated as a description of the trial’s design rationale or as evidence of observed power. Together, these limitations mean that the registry supports a description of the study but not a conclusion about efficacy or comparative safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Multi-Center Controlled Screening Trial of Safety and Efficacy of Lithium Carbonate in Subjects With Amyotrophic Lateral Sclerosis (ALS) — NCT00790582.
• Registry record last updated 2020-10-30; status last verified 2020-10.
• Results first posted 2020-10-30.
• 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.

18. Record Summary

The registry describes NCT00790582, a completed Phase II, single-group screening trial of lithium carbonate in people with amyotrophic lateral sclerosis. Enrollment is listed as 109; the study start is 2008-05 and primary completion is 2010-03. Allocation is listed as NA, masking as none, and the brief summary states there was no placebo.

The primary endpoint is change in the monthly rate of decline in ALSFRS-R, described as a 12-question functional questionnaire. The planned timeframe runs from baseline through Month 13. Vital Capacity is listed as a secondary outcome. The registry record reports 2 outcome measures and 0 analyses, and does not report numerical results for the primary endpoint.

Safety information lists affected counts, at-risk counts, deaths, historical controls, and leading serious-event terms. The record cautions that the historical-control groups are not a like-for-like comparison. Outcome interpretation is limited by the absence of posted analyses and by the single-group design.