A Two-Part Study of BOTOX® Therapy for Ischemic Digits: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Two-Part Study of BOTOX® Therapy for Ischemic Digits (NCT01309802), a randomized phase 2 study. The primary outcome is Percentage of Patient Reported Pain-free Days.

2. Clinical Question

The record identifies the study as a Phase 2 trial of BOTOX® therapy for ischemic digits. Its official title describes two parts: a 28-day randomized, double-blind, placebo-controlled clinical trial and a 5-year prospective outcomes study. The recorded primary outcome, however, is specifically framed over baseline to 28 days. The posted information does not give a separate numerical result for the longer-term prospective outcomes, nor does it show that the primary endpoint extended across the 5-year period.

The brief study description links the research question to relief of pain and healing of ulcerations, and also mentions quality of life. Those aims provide context for the trial, but the registry's primary endpoint is pain-free days. Secondary outcomes listed include pain-related quality of life, hand function, patient satisfaction, tissue perfusion, and EQ-5D health status. These measures address related but distinct questions; they should not be treated as interchangeable with the primary pain measure.

The central statistical question is therefore narrower than the full clinical motivation: how were the recorded pain-free-day values distributed between the randomized arms over the first 28 days, and how precisely can any difference be estimated from the posted results? The record gives an arm-level value of 12.0 for placebo and 48.0 for onabotulinum toxin type-A. It does not report a primary between-group estimate, confidence interval, or p-value. Consequently, the registry record permits a descriptive comparison of the posted arm values but does not establish the statistical uncertainty around that comparison.

3. Trial Design

This was a randomized, double-blind, parallel-group Phase 2 study sponsored by Southern Illinois University. The registry lists an enrollment of 48 and marks the study status as completed. The recorded start was 2011-05 and the primary completion date was 2016-05-19. Random allocation and double masking are design features intended to reduce systematic differences in treatment assignment and expectations, although the registry entries available for the posted results do not describe how randomization or masking was implemented.

The official title describes a 28-day controlled clinical trial followed by a 5-year prospective outcomes study. The primary outcome timeframe is baseline to 28 days, so the immediate randomized comparison should be interpreted separately from the longer prospective follow-up. The available record does not provide a numerical long-term outcome result, details of follow-up completeness, or an account of how the two study parts were linked analytically. These aspects are not reported in the registry record.

The active arm is named onabotulinum toxin type-A. Its description specifies up to 4 injections per hand, 100 units diluted in 2.0 mL normal saline per injection, a maximum of 360 units in a 3 month interval, and at least 28 days between injections during Study Year 1. The placebo arm is described as “no intervention.” The listed primary outcome arm records include 25.0 participants for placebo and 23.0 for the active intervention. These figures are presented as registry arm values; they should not be used to infer an analysis population or follow-up completion rate, neither of which is reported.

Randomized, double-blind, placebo-controlled parallel designs are generally used to support a fair comparison by assigning participants to concurrent groups while limiting knowledge of assignment. That is a general design principle, not a claim about unreported implementation details in this trial. The registry record does not report the random sequence method, allocation concealment, who was masked, or whether masking was maintained. It also does not report a sample-size justification or the planned primary statistical analysis. Accordingly, design labels describe the registered structure but cannot resolve those methodological details.

The primary endpoint was subjective and based on pain assessment. Subjective outcomes can capture a participant's lived experience, while also being sensitive to how questions are asked, recorded, and interpreted. The randomized and masked design is relevant to that measurement context, but the posted outcome record does not specify the scoring rules, analysis population, or handling of incomplete pain assessments. Those gaps constrain how far the reported arm values can be interpreted.

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

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.

Population: Race and Ethnicity were not collected for this protocol.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patient Reported Pain-free Days, measured over baseline to 28 days.

The primary outcome is titled “Percentage of Patient Reported Pain-free Days,” with a timeframe from baseline to 28 days. Its description refers to subjective pain scales—the visual analogue scale and faces pain assessment—and to participants reporting the total number of pain-free days within the 0-28 day period. The arm-level results are recorded as 12.0 for placebo and 48.0 for onabotulinum toxin type-A.

The endpoint is intended to represent how much of the early follow-up period participants experienced without pain. In general, a pain-free-days measure can complement a single pain rating because it describes symptom experience across a period rather than at one assessment moment. That is a general reason such an outcome may be useful; it does not establish how this particular endpoint was calculated or whether the values are averages, percentages aggregated across participants, or another summary. The registry labels the measure as a percentage and gives “NUMBER” as its parameter, but does not further define the calculation in the posted outcome information.

The description identifies participant-reported pain assessment, so the measure reflects subjective reports rather than an objective tissue measurement. That makes it directly relevant to a question about pain experience, while also making the measurement and analysis procedures important for interpretation. The registry record does not report the specific scale scoring rules, the method for converting reports into a percentage, the summary statistic, or the handling of missing daily assessments. It also does not post a primary between-arm effect estimate or its uncertainty. The recorded arm values therefore describe the posted endpoint results, but alone do not show how precisely the groups differed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies the trial as randomized, double-blind, and parallel-group. These terms describe the broad design: participants were assigned to groups at random, the study used double masking, and the groups were followed in parallel. In general, randomization can help balance both measured and unmeasured prognostic factors across groups, while masking can reduce the influence of expectations on care and outcome reporting. Those are general statistical principles. The record does not describe the randomization sequence, concealment, the people masked, or procedures for assessing whether masking was maintained.

What do the primary arm values tell us?

The primary outcome is a participant-reported pain-free-days measure over baseline to 28 days. The registry records 12.0 for placebo and 48.0 for onabotulinum toxin type-A. These values are not accompanied by a standard deviation, standard error, confidence interval, or primary p-value. The outcome is marked as “count other,” and the record notes that values are missing or not estimable for a two-arm comparison for this endpoint type. This means a recalculated two-arm comparison is not available from the posted primary summaries. The arm values should therefore be treated as descriptive rather than as a complete statistical test of the treatment contrast.

In general, an effect estimate describes the direction and size of a contrast, while a confidence interval expresses its uncertainty under a specified method. A p-value assesses compatibility between observed data and a null hypothesis under assumptions of a statistical model; it is not the probability that the null hypothesis is true. The primary result lacks the posted quantities needed to apply those inferential interpretations. No primary test or confidence interval should be inferred from the arm values alone.

How should the secondary comparison be read?

Patient Satisfaction is the secondary outcome with a posted two-arm comparison. Its registry summary records 3 events among 25.0 participants in placebo and 11 among 23.0 in the onabotulinum toxin type-A arm. The comparison is labelled as a risk difference, and the posted unadjusted p-value is 0.006. The risk difference compares the proportion with the outcome in one group with the proportion in the other. It is an absolute contrast, unlike a risk ratio or odds ratio, which express relative comparisons.

The posted comparison also includes a confidence interval and relative measures. The interval bounds and the risk-difference estimate are recorded with more than three decimal places, so they are not reproduced. Their direction is positive, and the interval bounds are both above zero. The p-value is unadjusted: it does not account for the fact that several outcomes or comparisons may have been considered. An unadjusted result can be informative, but it does not carry the same evidential weight as a prespecified primary analysis with a stated multiplicity strategy.

General caution applies to recalculated comparisons based on summary data. They can be useful as transparent, unadjusted descriptions, but may not match a trial's prespecified method, covariate adjustments, handling of missing observations, or analysis population. No sponsor-reported analysis is listed for this secondary endpoint. The registry record also does not describe a statistical plan that would establish whether this was a confirmatory comparison or an exploratory one.

Why does over-dispersion matter in general?

Over-dispersion occurs when observed variability in count data is greater than expected under a statistical model such as a simple Poisson model. If it is ignored, standard errors can be too small, which can make confidence intervals too narrow and p-values too optimistic. This is a general issue for count outcomes, not a method reported for this trial. The registry's primary outcome is categorized as “count other,” but it does not report a dispersion estimate or identify a count model. It would therefore be inappropriate to claim that over-dispersion was assessed or that a particular model was used.

For a pain-free-days outcome, the distribution may also depend on the way days and participant reports are aggregated. General statistical practice would define the unit of analysis, account for the outcome's bounds and distribution, and state how repeated or incomplete reports are handled. None of these analysis details is reported in the registry record. The data as posted do not allow readers to judge whether the chosen analysis addressed these considerations.

What are the planning illustrations?

The secondary satisfaction comparison includes planning illustrations based on fractions of the observed effect. These are hypothetical sample-size calculations, not evidence about the trial's observed power and not the trial's own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation, and a normal approximation. For planning for 100% of the observed effect, the illustration gives 25 participants per arm for 80% power and 33 participants per arm for 90% power. For planning for 75% of the observed effect, it gives 41 participants per arm for 80% power and 54 participants per arm for 90% power. For planning for 50% of the observed effect, it gives 80 participants per arm for 80% power and 107 participants per arm for 90% power.

These figures describe hypothetical future designs under the stated assumptions. They do not indicate the probability that this trial detected an effect, and they do not show that the trial was adequately or inadequately powered for its registered primary question. The sample-size justification for the actual trial is not reported in the registry record. Because the illustrations use the observed secondary satisfaction effect, they should not be mistaken for a calculation based on the primary pain-free-days endpoint.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists several secondary outcomes in addition to the primary pain-free-days measure. When a trial evaluates multiple outcomes or performs multiple comparisons, the probability of at least one nominally positive result can increase. This is the general statistical issue of multiplicity. Common approaches include predefining a hierarchy of outcomes, adjusting significance thresholds, or controlling an overall error rate. The registry record does not report a multiplicity plan, a testing hierarchy, or adjusted secondary results. The Patient Satisfaction comparison is explicitly unadjusted, so its p-value should be read as nominal rather than as a multiplicity-controlled finding.

The record reports no sponsor analyses for the posted secondary result and gives no reported analysis count. It does not state whether the trial had interim analyses, whether any outcome was changed after study start, or which analyses were prespecified. Those details are not reported in the registry record. Without them, it is not possible to judge whether the posted comparisons reflect a complete planned analysis or a subset of analyses.

Missing-data handling is also not described. The primary endpoint requires participant-reported pain information across a time window, but the record does not say how incomplete reports, missed assessments, or withdrawals were treated. It does not report an imputation method, a complete-case approach, or a sensitivity analysis. The arm-level counts alone should not be interpreted as proof that all randomized participants contributed usable endpoint data.

The analysis population is not stated. The record does not specify whether the primary analysis was intended to include all randomized participants, participants who received treatment, or another defined group. It also does not report exclusions after randomization or the reasons for any differences between enrolled and analyzed participants. Consequently, no intention-to-treat or per-protocol label should be assigned to the posted results.

These omissions matter because multiplicity, missingness, and analysis-population choices can affect both the estimated effect and its uncertainty. The randomized design is a strength in principle, but its interpretability depends on transparent reporting of how participants and outcomes entered the analysis. The registry record does not provide enough detail to assess those decisions for the primary endpoint or to establish confirmatory status for the unadjusted secondary result.

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: infection (8.0%), collapsed lung (4.3%), broken bone (4.0%), dizziness (4.0%), throat swelling (4.0%).

The registry lists serious adverse events for both arms and reports zero deaths in each. It records 5 serious adverse events for placebo, with 25 at risk, and 2 for onabotulinum toxin type-A, with 23 at risk. These are descriptive safety counts as recorded; they do not by themselves establish whether an event was caused by the intervention or whether the groups differ in underlying risk. The record does not provide a formal comparative safety analysis or uncertainty estimates.

The listed serious-event terms are Infection at 8.0%, Collapsed Lung at 4.3%, Broken bone at 4.0%, Dizziness at 4.0%, and Throat Swelling at 4.0%. The posted information does not map each listed term to a specific treatment arm or provide enough detail to interpret these percentages as arm-specific risks. They should not be treated as a ranked, causal account of treatment-related harms.

For other adverse events, the record reports 25 affected among 25 at risk in placebo and 22 affected among 23 at risk in the active arm. Such counts can help describe what was recorded, but the registry does not report event-level details, severity distribution, timing, attribution, or a statistical comparison. Safety assessment therefore remains descriptive and limited to the posted registry information. The absence of deaths in the record is not evidence that no other serious or clinically relevant risks occurred.

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

The posted primary results show different arm-level values for patient-reported pain-free days over baseline to 28 days: 12.0 for placebo and 48.0 for onabotulinum toxin type-A. They do not include a primary between-group estimate, confidence interval, or p-value. The primary result therefore describes the recorded summaries but does not quantify the uncertainty around the group contrast. It cannot, by itself, support a definitive statistical conclusion about the primary question.

The Patient Satisfaction secondary outcome has a recalculated unadjusted comparison with a positive risk-difference estimate, confidence interval limits above zero, and a p-value of 0.006. This is a nominal result for satisfaction, not a primary pain-free-days test. It is also one of several registered secondary outcomes, and the registry does not report multiplicity adjustment or sponsor-reported analyses. Its interpretation should therefore remain specific to that endpoint and calculation.

In general, a statistically notable result is not the same as a measure of clinical importance. Clinical relevance depends on what the outcome means, how it was measured, the size and precision of the effect, and the context in which it would be used. The registry does not report a threshold for a clinically meaningful change in pain-free days or satisfaction. It also does not provide enough information about endpoint construction and missing observations to fully interpret the measurement scale.

The trial's randomized, double-blind, placebo-controlled structure is relevant to evaluating a treatment comparison, but design labels do not replace complete results reporting. Important analysis details, including the primary statistical method, analysis population, missing-data procedures, and multiplicity strategy, are not reported in the registry record. The official title includes a 5-year prospective outcomes study, while the numerical primary outcome is limited to baseline to 28 days; long-term numerical results are not reported in the available record.

Accordingly, the results should not be converted into a general claim that the intervention works or does not work. They show what the registry records for the short-term primary endpoint and one secondary comparison, together with limitations in statistical detail. A fuller assessment would require the complete prespecified analysis and transparent reporting of all relevant outcomes and follow-up, which are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable because it combines a randomized, double-blind, placebo-controlled short-term comparison with a stated longer prospective outcomes component. That design creates a potentially useful framework for examining participant-reported pain and other outcomes over different time horizons. The record's primary endpoint is focused on pain-free days from baseline to 28 days, making the short-term question distinct from longer-term outcomes described in the official title.

The posted primary arm values illustrate why descriptive data and inferential results need to be distinguished. The two summaries are visibly different, but the registry does not report a primary contrast or its uncertainty. A careful statistical reading does not replace that missing analysis with an informal calculation, especially when the endpoint's summary method and variability are not described. The distinction helps prevent arm-level values from being mistaken for a complete test of the study question.

The secondary satisfaction result offers a contrasting example: a recalculated comparison is available, but it is unadjusted and does not answer the primary endpoint question. This emphasizes the importance of outcome hierarchy and multiplicity. In trials with several outcomes, a nominal secondary finding can be a useful signal for further examination, while still carrying less weight than a fully reported primary analysis.

The record also highlights the importance of documenting analysis populations, missing-data decisions, endpoint definitions, and follow-up results. These elements are necessary for assessing precision and potential bias, especially when outcomes depend on participant reports over time. They are not reported in the registry record for the primary comparison. Overall, the trial matters statistically as an example of why trial design labels, arm summaries, secondary comparisons, and complete inferential reporting must be considered separately rather than collapsed into one conclusion.

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 described as a percentage of patient-reported pain-free days, yet the description refers to reporting the total number of pain-free days over the 0-28 day period. The calculation connecting those descriptions is not stated. The outcome is also categorized as “count other,” and the record notes that values are missing or not estimable for a two-arm comparison. This leaves no posted primary effect estimate or inferential result to evaluate.

Second, the primary measure relies on subjective pain assessments using a visual analogue scale and faces pain assessment, but the registry does not provide scoring rules, timing of assessments within the period, aggregation procedures, or missing-report handling. The arm values are presented without a measure of variability or uncertainty. Their meaning is therefore less clear than it would be with a defined estimand, a fully specified summary, and a confidence interval.

Third, the official title refers to a 5-year prospective outcomes study, but the posted primary endpoint is limited to baseline to 28 days. The record does not provide numerical long-term results or details of long-term follow-up completion. No inference about persistence of pain relief, quality of life, or longer-term outcomes can be drawn from the short-term primary outcome values.

Fourth, the secondary satisfaction comparison is unadjusted and sits among multiple registered secondary outcomes. A multiplicity strategy is not reported. The comparison may be informative, but its nominal p-value should not be treated as conclusive evidence, particularly when no sponsor analysis is listed and the primary endpoint's inferential comparison is unavailable.

Finally, the registry does not report participant characteristics, primary analysis population, missing-data procedures, randomization implementation, or details of adverse-event attribution. These omissions limit assessment of generalizability, risk of bias, and safety. The listed adverse-event counts remain descriptive; they do not establish causation or provide a comparative safety estimate.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Two-Part Study of BOTOX® Therapy for Ischemic Digits — NCT01309802.
• Registry record last updated 2019-01-08; status last verified 2018-12.
• Results first posted 2017-06-02.
• 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

NCT01309802 is a completed Phase 2, randomized, double-blind, parallel-group study sponsored by Southern Illinois University. The registry reports an enrollment of 48 and a study start of 2011-05, with primary completion on 2016-05-19. The official title describes a 28-day placebo-controlled trial and a 5-year prospective outcomes study.

The primary outcome is percentage of patient-reported pain-free days from baseline to 28 days, assessed using subjective pain scales. The arm-level values are 12.0 for placebo and 48.0 for onabotulinum toxin type-A. A primary between-group estimate, confidence interval, and p-value are not reported in the registry record.

Patient Satisfaction is a secondary outcome with a recalculated unadjusted comparison and p-value of 0.006. The registry does not report multiplicity adjustment, the primary analysis plan, missing-data procedures, or analysis populations. Safety counts and listed serious-event terms are descriptive, with no formal comparative analysis reported.