A Study of the Effectiveness of Fampridine in Improving Upper Limb Function in MS: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the Effectiveness of Fampridine in Improving Upper Limb Function in MS (NCT02208050), a randomized phase 4 study. The primary outcome is Number of Participants Classified as Upper Limb Responders on the 9 Hole Peg Test (9HPT).

2. Clinical Question

The central statistical question is whether the posted results establish a difference between fampridine and placebo in this responder outcome. The registry record identifies the outcome and its measurement schedule, but does not report the responder counts, a treatment contrast, or an uncertainty interval. A comparison therefore cannot be characterized from the available record. The study also named the Jebsen Taylor Hand Function Test (JTT) and several mobility, arm-function, and quality-of-life measures as secondary outcomes. Their presence indicates a wider assessment program, but their results are not reported in the record.

3. Trial Design

This was a Phase IV, randomized, quadruple-masked, placebo-controlled crossover study sponsored by University College Dublin. The registry lists 64 participants as enrolled and the study as completed. Its target population was people with secondary progressive or primary progressive multiple sclerosis, with upper limb dysfunction described by a 9-HPT time between 15-90 seconds and Kurtzke EDSS scores in the range 4.0-7.0.

Participants were randomized to one of two treatment sequences. One sequence received fampridine for 8 weeks, underwent a 2 week washout, and then received placebo for 8 weeks. The other sequence received placebo first, underwent the washout, and then received fampridine. This arrangement means that the treatment comparison was intended to involve observations from both treatments in each participant, rather than separate groups receiving only one treatment.

General statistical context: In a crossover design, participants can serve as their own comparison, which can reduce the influence of stable differences between people. The design also requires attention to treatment order, changes over time, and whether effects persist into a later period. Randomizing the sequence helps distribute order effects, while a washout is intended to separate treatment periods. Whether the analysis accounted for period, sequence, or carryover effects, and how the washout was justified, are not reported in the registry record.

The primary outcome was a binary responder classification based on repeated 9-HPT assessments during treatment. The registry also lists secondary outcomes involving JTT responders, the 25 Foot Timed Walk, DASH, MSWS-12, AMSQ, and MSIS-29. The statistical methods used to compare these outcomes 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.

Baseline Assessment Period: 2 Weeks

Treatment Period 1: 8 Weeks Treatment

Washout Period 1: 2 Weeks

Reasons for not completing this period:

Treatment Period 2: 8 Weeks Treatment

Analysis population for the primary outcome, as defined in the registry: Analysis population included all participants who received treatment and placebo for eight weeks. Two participants withdrew during the second 8-week treatment period and were not included in the final 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 Number of Participants Classified as Upper Limb Responders on the 9 Hole Peg Test (9HPT), measured over 20 weeks. Baseline assessments 1,2,3: weeks 0-2. Assessment 4 - midway through first treatment period; assessment 5: end of first treatment period. Assessment 7: midway through second treatment period, assessment 8: end of second treatment period..

The primary endpoint was the number of participants classified as upper limb responders on the 9 Hole Peg Test. The 9-HPT measures timed performance as a participant places 9 pegs on a pegboard and removes them, with time recorded separately for each hand. Longer completion time indicates poorer upper limb function.

The registry defines a 20% improvement as a 20% shorter time in seconds. To qualify as a responder, a participant had to show that improvement on both of the two on-treatment assessments, compared with the average of baseline assessments 1, 2, and 3. The on-treatment assessments were assessments 4 and 5 in the first treatment period or assessments 7 and 8 in the second period. The washout assessment was not included in the analysis.

General statistical context: Converting a timed test into a responder outcome can make the result easier to interpret as a count of participants meeting a prespecified criterion. It also reduces the detail available from the original times: participants just below and well above the threshold are both counted as responders, while those just short of it are classified as nonresponders. The record does not report the responder counts or the treatment comparison, so the endpoint definition alone does not show how participants performed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, quadruple-masked crossover trial, but it does not report the statistical analysis plan or the specific methods used to estimate treatment effects. The general explanations below describe statistical considerations relevant to this design; they should not be read as claims about methods actually used in the trial.

What does randomization contribute?

General: Random assignment of treatment sequence is intended to reduce systematic differences between sequence groups. In this study, one sequence began with fampridine and the other with placebo. Randomization does not itself guarantee that all potential sources of bias or imbalance are removed, and it does not specify how the final comparison was calculated. The randomization procedure, allocation concealment details, and any stratification are not reported in the registry record.

Why use a crossover design?

General: In a crossover study, each participant can contribute observations under both treatments. The analysis can use the within-participant contrast, accounting for the fact that repeated observations from the same person are correlated. Stable participant characteristics are then less likely to explain a treatment contrast than in a comparison of separate groups. However, the design depends on treatment effects being interpretable across periods. Changes over time, treatment order, and effects persisting after a period ends can complicate interpretation. The registry describes a 2 week washout between treatment periods, but does not report the rationale for its duration or the analysis of potential carryover.

How is the primary outcome constructed?

The endpoint is a binary classification derived from timed 9-HPT assessments. The test records the time taken to place and remove 9 pegs, with longer time indicating poorer upper limb function. A 20% improvement is defined in the record as a 20% shorter time. A participant is a responder only if both on-treatment assessments meet the improvement criterion relative to the average of baseline assessments 1, 2, and 3. Assessments 4 and 5 or assessments 7 and 8 supply the two on-treatment measurements, and the washout assessment is excluded.

General: A binary endpoint simplifies the comparison to responder counts or proportions. It can be useful when a threshold has a meaningful interpretation, but it discards information about the size of changes in measured time. The record does not provide the count classified as a responder under either treatment, or a model or test for comparing those outcomes. It also does not report whether hand-specific times were handled separately or combined in any particular way.

What would precision and significance measures add?

General: An estimated treatment contrast describes the observed difference under a stated analysis. A confidence interval expresses the uncertainty around that estimate under the model assumptions. A significance test assesses compatibility with a null value, but it does not replace the estimate or its interval. For a crossover comparison, these quantities depend on the paired data and on how treatment period and sequence are handled. Since no primary estimate, interval, or p-value is reported in the registry record, the precision of the treatment comparison cannot be assessed.

How should planning estimates be read?

The stated planning assumptions describe an illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrated effect is a stated fraction of the observed effect. The registry record does not report the numerical sample-size estimates or the observed effect needed to interpret those illustrations. In general, a planning estimate is conditional on its assumptions and is not evidence that a trial had a particular probability of finding an effect. A sample-size illustration must not be confused with observed power, which would not establish the precision of the actual result.

The record does not report the trial's own sample-size justification, model specification, treatment-effect estimator, variance method, handling of repeated measurements, interim analyses, or multiplicity adjustment. These omissions prevent independent assessment of whether the actual analysis followed a prespecified plan or adequately reflected the crossover structure.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary 9-HPT responder outcome and secondary outcomes covering JTT responder status, mobility on the 25 Foot Timed Walk, DASH, MSWS-12, AMSQ, and MSIS-29. It also reports seven outcome measures. Considering multiple outcomes can create multiplicity: when many statistical comparisons are made, the chance of at least one apparently notable result may increase. General statistical context: Researchers may address multiplicity through a prespecified testing order, adjustment, or careful emphasis on estimation rather than isolated significance tests. Whether any approach was used is not reported in the registry record.

The registry does not report a statistical analysis plan, a hierarchy among secondary outcomes, adjustment for multiple comparisons, or outcome-specific analysis methods. It is therefore not possible to tell whether the primary endpoint was the only confirmatory test or how results across outcomes were intended to be interpreted. The record also does not provide estimates for the listed secondary outcomes.

The primary analysis population included participants who received both treatment and placebo for eight weeks. Two participants withdrew during the second 8-week treatment period and were not included in the final analysis. The record does not describe the amount or pattern of missing outcome data, the reason for these withdrawals, or any imputation or sensitivity analysis. It does not report whether participants with other incomplete assessments were excluded or retained for particular analyses. These details matter because exclusions and missing observations can affect both the analyzed population and the reliability of a crossover comparison.

The term intention-to-treat is not used in the registry's population description, and the record does not state that all randomized participants were included in the primary analysis. It would therefore be inappropriate to characterize the reported population as a specific analysis set beyond the record's own description.

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 non-serious adverse event terms

The registry lists serious adverse event figures separately for fampridine and placebo. For each treatment, 64 participants were at risk, zero were recorded as affected by serious adverse events, and zero deaths were listed. For other adverse events, 32 participants were recorded as affected during fampridine and 25 during placebo, with 64 at risk in each treatment listing.

These figures are counts of participants affected as recorded, not a complete description of event types, timing, duration, severity, or recurrence. The registry record does not list serious adverse event terms. The other adverse event totals are not broken down by event type in the registry record for this account, so they cannot show which events were involved or how they were assessed.

General statistical context: In a crossover study, participants may contribute exposure to both treatments. Treatment-specific counts should not automatically be treated as counts from independent groups of people. The registry lists 64 at risk under each treatment, but does not explain the adverse-event analysis conventions or provide a paired comparison. These descriptive counts alone do not establish a causal safety difference, and zero recorded serious adverse events does not mean that no adverse events of any kind occurred.

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

The record gives a clear operational definition of the primary outcome and describes a randomized, masked crossover comparison of fampridine and placebo. It identifies the target population as people with secondary progressive or primary progressive multiple sclerosis and upper limb dysfunction, and describes the sequence and duration of treatment periods. These features make the study question and measurement approach understandable.

However, the registry record does not report the primary responder counts or a statistical comparison. It is not possible to state whether the primary outcome favored either treatment, how large any difference was, or how precisely it was estimated. The endpoint definition cannot substitute for observed outcome data. The adverse-event counts are descriptive and do not answer the primary efficacy question.

General statistical context: A trial result is interpreted from the estimated effect, its uncertainty, the analysis population, and the assumptions underlying the analysis. A responder threshold describes who qualifies for a category, but does not reveal how many participants qualified. Likewise, a completed trial and a specified design do not by themselves establish the result of the treatment comparison.

The record also does not report how the crossover analysis handled period or sequence effects, missing data, or multiplicity. Those details could affect interpretation of a treatment contrast. The listed secondary outcomes broaden the range of measurements, but without their results and analysis methods they cannot confirm, qualify, or contradict the primary outcome.

Accordingly, the defensible reading is limited: this registry describes a trial designed to examine upper limb function using a responder definition based on repeated 9-HPT measurements, but the posted information described in this record is insufficient to determine the comparative outcome. No claim that fampridine improved or failed to improve upper limb function follows from these data alone.

13. Why This Trial Matters Statistically

This trial is statistically notable for pairing a binary responder endpoint with a crossover design. The primary outcome turns repeated timed 9-HPT measurements into a count of participants meeting a stated improvement threshold. The crossover structure means that participants were scheduled to receive both fampridine and placebo, with treatment order randomized and a washout between periods.

General statistical context: This design can make within-person comparisons informative because stable differences between participants do not vary across their treatment periods. At the same time, repeated observations are dependent, and the order and timing of treatment can matter. A sound interpretation therefore relies on a clearly described analysis that reflects the paired structure and addresses period, sequence, and potential carryover effects. The registry record does not report those methods.

The responder definition also highlights a common statistical trade-off. A threshold-based endpoint can be readily communicated as a count of participants meeting a criterion, but it compresses the underlying continuous timing data into categories. Its interpretation depends not only on the threshold but also on the reported counts and comparative estimate. Those outcome results are not reported in the record.

The entry is useful for identifying what was intended to be measured, how the treatment periods were arranged, and which population was described. It also makes clear why registry design information and posted results are distinct: an outcome definition does not provide an observed treatment effect. For readers assessing statistical evidence, this distinction prevents a detailed protocol description from being mistaken for evidence about the magnitude or precision of a 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 main limitation for interpretation is that the registry record does not report the primary responder counts or a treatment-effect estimate. Without these, the direction, size, and precision of the primary comparison cannot be assessed. The record also lists no statistical analyses, so it does not provide a test result or confidence interval to interpret.

The crossover design introduces considerations that cannot be evaluated from the registry entry. The statistical approach to repeated observations, treatment period, sequence, and possible carryover is not reported. The 2 week washout is described, but its rationale and adequacy are not given. The record does not specify the model, estimator, or assumptions used for comparing treatments.

The analysis population excluded two participants who withdrew during the second 8-week treatment period. The record does not give withdrawal reasons, explain how missing measurements were handled, or report sensitivity analyses. It also does not state whether all randomized participants were included in analyses other than the described population.

Several secondary outcomes are listed, but their results, analysis methods, and any adjustment for multiple comparisons are not reported. This prevents assessment of how multiple endpoints were interpreted alongside the primary outcome. Finally, the safety figures are summary counts without event terms or a reported comparative analysis. They describe recorded affected participants but cannot resolve the efficacy question or provide a detailed safety profile.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study of the Effectiveness of Fampridine in Improving Upper Limb Function in MS — NCT02208050.
• Registry record last updated 2021-07-09; status last verified 2021-07.
• Results first posted 2021-07-09.
• 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 a completed Phase IV, randomized, quadruple-masked, placebo-controlled crossover study sponsored by University College Dublin, with 64 enrolled participants. The population was people with secondary progressive or primary progressive multiple sclerosis and upper limb dysfunction. Participants received fampridine and placebo in opposite treatment sequences, with an 8 week treatment period for each and a 2 week washout between them.

The primary outcome was the number of participants meeting a defined 9-HPT responder criterion based on two on-treatment assessments and baseline measurements. The record lists secondary outcomes involving JTT, walking, arm function, and multiple sclerosis measures. Two participants withdrew during the second 8-week treatment period and were not included in the final analysis.

Serious adverse events and deaths were listed as zero under both treatments; other adverse events affected 32 participants during fampridine and 25 during placebo. The primary outcome results, statistical comparison, analysis methods, and handling of missing data are not reported in the registry record.