Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer's Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer's Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44 (NCT00948766), a randomized phase 4 study. The primary outcome is Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24.

2. Clinical Question

The record describes a randomized, parallel-group, double-blind core study, followed by a 24-week open-label extension. The primary question concerns the core study only, not the extension. The extension offered additional safety and efficacy follow-up and switched completers to the higher-dose patch, so it does not provide the same randomized comparison as the core study.

3. Trial Design

This was a phase 4, randomized, parallel-group study sponsored by Novartis. The registry lists quadruple masking. The core study was prospective, multicenter, and double-blind, and compared rivastigmine patch 13.3 mg/24 h with rivastigmine patch 4.6 mg/24 h over 24 weeks. The registry reports enrollment of 716. The study started in 2009-07, had primary completion in 2012-01, and is marked completed.

The primary outcome was assessed from core-study baseline to Week 24. The primary analysis included 310 participants in the 13.3 mg/24 h group and 303 in the 4.6 mg/24 h group. Those analysis counts are not the same as the overall enrollment: the primary analysis population was restricted to randomized participants who received at least one dose and had at least one post-baseline measurement of the co-primary efficacy variables, with only available data included.

The core-study description says participants assigned to 13.3 mg/24 h were titrated in steps. The complete schedule for that arm is not reported in the registry record. The 4.6 mg/24 h group received that dose throughout the core study, with placebo also listed in the description for later weeks. The interventions list includes 9.5 mg/24 h and placebo as well as the two comparison doses, but the reported primary comparison is between the 13.3 mg/24 h and 4.6 mg/24 h groups.

The extension lasted an additional 24 weeks and was open label. According to the study summary, participants completing the core study received the higher-dose patch during the extension. Extension findings therefore address continued follow-up under a different treatment arrangement and should not be read as an extension of the original randomized dose comparison.

The registry record does not report the original sample-size justification, detailed allocation procedures, or the rationale for the masking label. These details should not be inferred from the study title or the posted results.

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: One patient in each treatment group in the core study and one patient in the treatment group in the extension study did not receive study medication; they were not included in the safety set.

Core Study

Reasons for not completing this period:

Extension Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified full analysis set: All randomized patients who received at least 1 dose of study medication and had at least 1 post-baseline measurement of the co-primary efficacy variables. Only patients with available data were included in the analysis.

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 Core Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24, measured over Baseline of the core study to Week 24 of the core study.

The primary endpoint was change from baseline to Week 24 in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version score, abbreviated ADCS-ADL-SIV. It is a caregiver-interview measure intended to capture both basic and instrumental daily activities. Examples in the registry description include personal care, communication and interaction, household tasks, hobbies and interests, and judgments and decisions.

The instrument has 19 questions, with responses based on forced choices or yes/no answers and additional sub-questions. The total score ranges from 0 to 54. A higher total score represents higher functioning, and a positive change score indicates improvement. Thus, the endpoint is oriented so that a positive change is improvement, while a negative mean change represents a decline in the measured score over the interval.

Daily functioning is relevant to severe dementia because the measure focuses on activities that can be observed and discussed with a caregiver. Its use makes the primary question about functioning rather than only cognition or a broad clinical impression. It is a continuous score, so the posted primary result compares group mean changes and their uncertainty. The registry record does not report a threshold for interpreting how large a change would be important to patients or caregivers.

7. Results Posted in the Registry

• Rivastigmine 4.6 mg/24 h Transdermal Patch: mean -3.60 versus -2.60 on control; difference -1.00 (95% CI -2.15 to 0.15), standardized effect d = -0.14; z-test p = 0.089.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Rivastigmine 4.6 mg/24 h Transdermal Patch: mean 1.20 versus -0.40 on control; difference 1.60 (95% CI -0.82 to 4.02), standardized effect d = 0.10; z-test p = 0.196.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Rivastigmine 4.6 mg/24 h Transdermal Patch and the control. The interval gives the range of effects that remain compatible with the data.

The registry names several secondary outcomes, including clinical global change, neuropsychiatric symptoms, daily functioning during the extension, and cognition during the extension. Among the secondary results with numerical comparisons in the record, the NPI-12 change comparison has an estimated mean difference of 1.6, a confidence interval from -0.823 to 4.023, and an unadjusted p-value of 0.196. Its interval includes zero, and the score-direction interpretation is not described in the listed endpoint details.

The other named secondary outcomes do not have numerical results reported in the registry record. Consequently, a consistent pattern across all secondary endpoints cannot be assessed from the posted results. The primary endpoint remains the clearest numerical result for the core-study question; the NPI-12 comparison does not resolve the uncertainty in the primary comparison. Extension outcomes also differ in design context because the extension was open label and offered the higher-dose patch to core-study completers.

Secondary outcomes can help describe whether findings are reflected across different kinds of assessment, but they are not interchangeable measures. A daily-function score, a neuropsychiatric inventory, and a clinical global-change assessment address different constructs and can have different scales and directions. A numerical contrast on one should not be treated as a direct confirmation or contradiction of another without considering those distinctions.

The reported secondary p-value is unadjusted. When multiple outcomes are examined, some results may appear statistically notable by chance even if there is no corresponding underlying difference. Without a reported multiplicity plan, the secondary results carry less evidential weight than a prespecified primary result analyzed under a stated plan. The registry record does not report whether any secondary outcome was designated as confirmatory or how the family of tests was defined.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Core Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24
• Core Study: Change From Baseline in the Neuropsychiatric Inventory (NPI-12) Score at Week 24
• Extension Study: Change From Baseline in the Alzheimer's Disease Cooperative Study-Activities of Daily Living-Severe Impairment Version (ADCS-ADL-SIV) Score at Week 24
• Extension Study: Change From Baseline in the Severity Impairment Battery (SIB) Score at Week 24
• Extension Study: Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC) Score at Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

The reported primary endpoint is continuous: each participant has a score, and the posted group summaries use means and standard deviations. A mean gives the average score change within a group. A standard deviation describes how spread out individual changes are around that group mean. These quantities answer different questions. The standard deviation reflects participant-to-participant variability; the confidence interval for the contrast reflects uncertainty about the estimated difference between group means.

What does the mean difference represent?

The registry reports the contrast as the 4.6 mg/24 h group relative to the 13.3 mg/24 h group. The estimated mean difference is -1.0. Because the primary score defines positive change as improvement, the separate group means are important context: they are -2.6 and -3.6, respectively. The contrast is a comparison of average changes, not a statement that each participant changed by that amount. Nor does it reveal how many participants improved, stayed the same, or declined.

Direction depends on both the order of the groups in a contrast and the outcome's scoring convention. A negative contrast does not automatically mean harm or benefit. It must be read alongside the group labels and the definition of the scale. For this primary measure, the group with the higher dose had a less negative mean change, but the uncertainty around the estimated contrast means that this numerical ordering alone is not conclusive.

Why use a confidence interval?

A confidence interval gives a range of values compatible with the observed data under the statistical model used to construct it. It conveys both the estimate and its precision. A narrow interval indicates greater precision than a broad one, while an interval that includes zero leaves open the possibility of no mean difference. The primary interval runs from -2.151 to 0.151, crossing zero. This is consistent with the unadjusted p-value of 0.089: the posted comparison does not meet the conventional two-sided 0.05 threshold. That threshold is a statistical convention, not a boundary between a real and unreal effect.

The interval does not give the probability that the true difference is within the particular range, and it does not show that all values in it are equally plausible. Its interpretation depends on the model and analysis assumptions. The registry record does not report the full statistical analysis plan or enough detail to independently evaluate all of those assumptions.

How should the p-value be read?

A p-value measures how inconsistent the observed data, or data more extreme, would be with a specified null model. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The unadjusted p-value of 0.089 is associated with the primary comparison as posted. It should be read together with the estimate and confidence interval, rather than used as a stand-alone verdict.

“Unadjusted” matters because the registry record does not report an adjustment for testing multiple outcomes or comparisons. When many tests are conducted, the chance of seeing at least one apparently unusual result can rise. An adjustment can address that issue, but the choice of method and the family of tests to be considered must be specified. The record does not report those details, so the p-values should not be treated as multiplicity-controlled evidence.

What does variability add?

The primary group standard deviations were 6.82 and 7.68. They show that individual changes varied substantially around the group averages. A mean difference can be estimated even when individual outcomes are variable, but the variability affects how precisely that difference is estimated. The standard error is one way to express sampling uncertainty for a mean; it is not the same as the standard deviation. The registry-derived comparison includes a pooled standard deviation of 7.258, while the confidence interval expresses uncertainty in the group contrast.

General statistical point: over-dispersion occurs when data vary more than a model assumes. If a model underestimates variability, its uncertainty estimates can be too small and its confidence intervals too narrow. The primary endpoint is summarized as a continuous measure with means and standard deviations; the registry record does not report evidence of over-dispersion or the diagnostic procedures used to assess model assumptions. It would therefore be inappropriate to claim that over-dispersion occurred or that a particular correction was used.

What can be inferred from the analysis population?

The primary population is described as a modified full analysis set. It includes randomized participants who received at least one dose and had at least one post-baseline measurement of the co-primary efficacy variables; only participants with available data were included in the analysis. This definition indicates that the reported analysis was not simply every person enrolled. It also means the result is conditional on meeting those analysis criteria. The exact handling of missing observations, any imputation, and any sensitivity analyses are not reported in the registry record.

Randomization is intended to make treatment groups comparable at assignment, on average, but analysis exclusions and missing data can affect the comparability of the analyzed groups. The posted participant counts and estimate describe the registry's analysis population. Without fuller information about missingness and analysis procedures, the degree to which those issues affect the estimate cannot be assessed from the registry record alone.

What is an unadjusted recalculation?

Where a recalculated comparison is presented, it is a simple unadjusted calculation from the posted summary statistics. It is not a substitute for the sponsor's full analysis and does not account for unreported covariate adjustment, stratification, repeated-measures modeling, or other features of a prespecified analysis. The registry record does not report those details for the primary result. No discrepancy is flagged between the recalculated comparison and the posted comparison, but the posted result remains the basis for interpretation.

11. Confidence Intervals and Precision

The primary estimate is a mean difference of -1.0, with a confidence interval from -2.151 to 0.151. This interval is the clearest indication of the precision of the posted contrast. It includes zero and extends to values on either side of zero, so the data do not sharply distinguish a small difference in one direction from no difference or a difference in the other direction. The interval's width reflects meaningful uncertainty about the size of the mean contrast.

Precision is distinct from whether a result passes a significance threshold. A p-value of 0.089 does not tell readers whether the estimated difference is large enough to matter; the interval shows a range of compatible values under the analysis. The interval also cannot establish that every value it contains is equally likely. Interpretation depends on the design and statistical assumptions, some of which are not reported in the registry record.

The primary group standard deviations, 6.82 and 7.68, indicate the spread of individual changes. They should not be confused with the confidence interval or with the uncertainty in the mean difference. Participants' individual trajectories can vary much more than the group-average contrast, and the mean alone does not describe that distribution.

The secondary NPI-12 estimate is also imprecise: its confidence interval runs from -0.823 to 4.023 and includes zero. The unadjusted p-value is 0.196. Results for the other named secondary outcomes are not reported in the registry record, so precision across the full set of secondary outcomes cannot be assessed. The registry record also does not report a clinically important difference threshold for the primary scale. Statistical precision alone therefore cannot establish whether any possible difference would be meaningful to patients or caregivers.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are participants per arm, not total participants across both arms and not total events. They are illustrations based on the observed effect, rather than a report of the trial's original sample-size calculation. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each scenario targets a stated fraction of the observed effect.

The 80% power column gives the number of participants per arm that the planning calculation estimates would be needed to have an 80% chance of detecting the specified effect under those assumptions, if that effect were the true one and the model assumptions held. The 90% column gives the corresponding estimate for a 90% chance. These are planning concepts, not guarantees about what a future study will find. They do not describe the power actually achieved in this trial.

For the primary endpoint, planning for 100% of the observed effect gives 827 participants per arm for 80% power and 1,107 participants per arm for 90% power. Planning for 75% of the observed effect gives 1,471 participants per arm for 80% power and 1,968 participants per arm for 90% power. Planning for 50% of the observed effect gives 3,308 participants per arm for 80% power and 4,428 participants per arm for 90% power. The listed values illustrate the central relationship: smaller effects require more participants to detect with the same target power.

These are sample-size planning illustrations, not observed power. The trial's original sample-size justification and design assumptions are not reported in the registry record. Planning from an observed effect can be especially uncertain because that estimate itself has sampling error; the figures should not be treated as a definitive prescription for a future study.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -1.000; pooled standard deviation σ = 7.258.
2. n = 2 × (1.96 + 0.842)² × 7.258² / -1.000² = 826.9, rounded up to 827 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -1                      # observed difference in means
sigma <- 7.25782115523938                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(948766)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 827 (80% power), 1,107 (90% power)
 75% of observed effect: n per arm = 1,471 (80% power), 1,968 (90% power)
 50% of observed effect: n per arm = 3,308 (80% power), 4,428 (90% power)
power.t.test: 827.9 
Simulated power at n = 827 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

The study lists a primary outcome and multiple secondary outcomes, including outcomes measured in both the core study and the extension. Testing several outcomes creates a multiplicity issue: the more hypotheses examined, the greater the chance that at least one will appear unusual by chance. General statistical practice addresses this by defining the relevant family of tests and, when appropriate, adjusting the testing procedure or interpreting secondary analyses as exploratory.

The registry record does not report a multiplicity adjustment, a hierarchy for testing outcomes, or a prespecified plan identifying which secondary comparisons were confirmatory. The posted p-values are unadjusted. They should therefore be read as nominal results rather than as evidence that an overall family-wise error rate was controlled. The absence of a reported adjustment does not establish that none was used outside the registry; it means the procedure is not reported in the registry record.

The primary population is a modified full analysis set: randomized participants who received at least one dose and had at least one post-baseline measurement of the co-primary efficacy variables. The record also states that only participants with available data were included. The primary group counts are 310 and 303, while overall enrollment is 716. These different counts reflect different denominators and should not be conflated.

The registry record does not report the amount or pattern of missing primary outcome data, the reasons for missingness, the method used to handle missing measurements, or sensitivity analyses assessing the impact of missing data. General statistical concern: if missingness is related to a participant's outcome or treatment experience, analyzing only available observations can produce a biased estimate. Whether that concern affected this result cannot be established from the registry information.

Other details that would help evaluate the analysis, including the original statistical analysis plan, covariate adjustments, and any interim analyses, are not reported in the registry record. The trial's original sample-size justification is also not reported. These omissions limit assessment of whether the posted analyses followed a prespecified plan and how robust the primary estimate is to alternative reasonable methods.

15. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: urinary tract infection (2.0%), fall (2.0%), syncope (2.0%), dehydration (1.7%), agitation (1.7%).

The registry lists serious adverse event counts for the core-study groups and for the extension group. In the core study, 82 of 355 participants in the 13.3 mg/24 h group and 74 of 359 participants in the 4.6 mg/24 h group are listed as affected by serious adverse events. In the extension, 79 of 396 participants in the 13.3 mg/24 h group are listed. These are counts of participants affected among the listed numbers at risk; they are not counts of all individual event episodes.

The most frequently listed serious terms include urinary tract infection, fall, and syncope, each at 2.0%, and dehydration, agitation, and mental status changes, each at 1.7%. The registry also lists other adverse events affecting 216 of 355 and 210 of 359 participants in the core groups, and 248 of 396 in the extension group. The record does not report death counts in these safety results.

The extension group is not a randomized comparison against a concurrent lower-dose group in the posted description: completers received the higher-dose patch during the open-label extension. The core and extension counts therefore should not be compared as though they arose from the same randomized contrast. These registry figures describe reported safety counts; they do not by themselves establish causation or provide a complete assessment of risks.

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

The primary endpoint addresses a specific question: how the mean change in daily-function score differed between two rivastigmine patch groups during the 24-week core study. The posted means were -2.6 for the 13.3 mg/24 h group and -3.6 for the 4.6 mg/24 h group. The estimated difference was -1.0 when expressed as the lower-dose group relative to the higher-dose group. The confidence interval includes zero, so the size and direction of the underlying mean difference remain uncertain.

This finding does not establish that the groups had identical outcomes. A confidence interval that includes zero can reflect uncertainty broad enough to accommodate no difference and differences in either direction. Conversely, the numerical ordering of the means does not establish a reliable difference. Both statements matter: the registry does not provide a precise estimate, and absence of a conventionally significant result is not proof of equivalence.

The result is about an average score change, not an individual participant's course, and the registry record does not report a threshold for a clinically important change on the scale. It therefore cannot determine whether a possible difference would be noticeable or meaningful to patients and caregivers. The score assesses daily activities, but it does not encompass every aspect of dementia or treatment experience.

The estimate applies to the described analysis population, not necessarily every randomized participant or every person with severe dementia. It also concerns the core-study comparison. The open-label extension, in which completers received the higher-dose patch, does not preserve the same randomized dose contrast. The posted core-study result should not be extended to a claim about longer-term comparative effects.

More generally, trial results depend on the study population, treatment assignment, outcome definition, follow-up, and analysis methods. Some relevant analysis details, including missing-data procedures and multiplicity handling, are not reported in the registry record. The statistical evidence should therefore be read as a bounded description of the posted comparison, not as a complete account of all possible outcomes or as medical advice.

17. Why This Trial Matters Statistically

This study illustrates why the point estimate alone is not enough. The two primary group means differ numerically, and the estimated contrast is -1.0, but the confidence interval includes zero and the unadjusted p-value is 0.089. Reading the estimate together with its interval makes the uncertainty visible. A directionally ordered pair of means is not, by itself, strong evidence of a precise between-group difference.

It also illustrates the distinction between observed sample size and analysis population. Overall enrollment was 716, while the primary analysis included 310 and 303 participants in the two groups. The registry's modified full analysis set definition clarifies that treatment exposure and post-baseline measurement were required. Those distinctions are essential for interpreting who contributed to the primary estimate.

The trial's secondary outcomes and open-label extension provide additional context, but they do not replace the primary randomized contrast. Multiple endpoints raise multiplicity concerns, and the extension's treatment arrangement differs from the core study. Unadjusted secondary findings and extension observations should not be treated as if they were independent confirmatory tests of the primary question.

Finally, the record distinguishes what can be read from posted summaries from what remains undocumented. The score direction, group means, confidence interval, and analysis-population definition are explicit. The original sample-size justification, missing-data procedures, and multiplicity plan are not reported in the registry record. Keeping those boundaries clear is part of sound statistical interpretation: describe the evidence and its precision without filling gaps through assumptions.

18. 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 comparison is reported as group means and standard deviations, but the registry record does not include the full statistical analysis plan. Details such as covariate adjustment, any repeated-measures approach, and model diagnostics are not reported in the registry record. The available summaries therefore do not allow a complete independent reconstruction of the sponsor's analysis.

The modified full analysis set excludes randomized participants who did not meet the stated treatment-exposure and post-baseline measurement criteria. Only available data were included. The record does not report how many participants were excluded for each reason, the pattern of missing measurements, or whether missingness differed between groups. It also does not describe imputation or sensitivity analyses.

The primary outcome is a caregiver-interview scale, and its interpretation depends on the instrument and the information available from caregivers. The record describes the scale and its scoring direction but does not report a threshold for clinical importance. The estimated difference therefore cannot be translated from the registry summaries into a claim about the practical importance of a change.

Only one secondary outcome has a numerical comparison in the listed results, while several others are named without numerical results reported in the registry record. The secondary p-value is unadjusted, and the multiplicity plan is not reported. This limits the ability to assess the coherence and confirmatory status of secondary findings.

The extension was open label and offered the higher-dose patch to core-study completers. Its safety and efficacy observations do not provide the same randomized comparison as the core study. The registry record also does not report the trial's original sample-size justification or detailed procedures for allocation and masking. These limitations constrain interpretation of precision, robustness, and generalizability.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Effects of Rivastigmine Patch on Activities of Daily Living and Cognition in Patients With Severe Dementia of the Alzheimer's Type (ACTION) (Study Protocol CENA713DUS44, NCT00948766) and a 24 Week Open-label Extension to Study CENA713DUS44 — NCT00948766.
• Registry record last updated 2013-08-28; status last verified 2013-08.
• Results first posted 2013-02-11.
• 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.

22. Record Summary

The registry describes a completed phase 4 randomized, parallel-group, double-blind core study of rivastigmine patches in people with severe dementia of the Alzheimer's type, followed by a 24-week open-label extension. The primary endpoint was change in ADCS-ADL-SIV score from core-study baseline to Week 24. Positive change indicates improvement.

Mean changes were -2.6 with the 13.3 mg/24 h patch and -3.6 with the 4.6 mg/24 h patch. The estimated mean difference was -1.0; its confidence interval included zero, and the unadjusted p-value was 0.089. The result is therefore uncertain in size and direction. The record also includes one numerical secondary comparison and safety counts, while several other named secondary results are not reported in the registry record.

The original sample-size justification, multiplicity plan, and detailed missing-data methods are not reported in the registry record. The extension's open-label design should be distinguished from the randomized core comparison.