CD-PROBE: Cervical Dystonia Patient Registry for the Observation of onabotulinumtoxinA Efficacy: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for CD-PROBE: Cervical Dystonia Patient Registry for the Observation of onabotulinumtoxinA Efficacy (NCT00836017), a registered phase not stated study. The primary outcome is Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score.

2. Clinical Question

The clinical question concerns the recorded symptom burden among people receiving treatment in usual clinical practice, rather than a randomized comparison of treatment against a control. TWSTRS combines ratings of severity, disability, and pain. Its total score ranges from 0, least symptoms, to 85, worst symptoms; higher scores indicate greater symptom severity. The registry description therefore defines a measure of cervical dystonia impact, but the record does not provide the observed mean, its variability, or a comparison with a baseline value.

The registry lists secondary outcomes concerning mild disease severity, clinician and patient global impressions of change, and pain. These are additional descriptive questions, not substitutes for a controlled comparison. Without reported outcome estimates and an analysis plan, the record cannot establish how participants' scores changed or whether any change was attributable to treatment.

3. Trial Design

CD-PROBE is an observational registry for the observation of onabotulinumtoxinA efficacy in cervical dystonia. The record lists enrollment of 1046 and status as completed. The study start is recorded as 2009-01 and primary completion as 2013-08. Allergan is listed as the sponsor.

Although the registry identifies a BOTOX® group, it states that treatment was prescribed by physicians as standard care in clinical practice and that no intervention was administered as part of the study. This distinction matters: the registry observed clinical care rather than assigning participants to study treatment. The allocation field is not stated, and the record warns that the arms are not a like-for-like control comparison. There is no randomized control group described in the record.

The primary outcome is the mean TWSTRS total score at 4-6 weeks after treatment 3, with the timeframe also described as up to 104.3 weeks. The outcome population is all participants with data available for this measure at all visits. This wording identifies a data-availability condition for inclusion in the outcome population, but does not explain how many participants met it or how missing measurements were handled.

The registry lists five outcome measures, including the primary TWSTRS outcome and secondary measures of severity, global impression of change, and pain. It lists zero analyses. Consequently, the record does not provide numerical outcome findings, statistical estimates, or details of the analyses used to assess them. It also does not report a protocol rationale for the enrollment size, an interim-analysis plan, or a complete statistical analysis plan.

In an observational registry, participants' care and characteristics may differ for reasons that are not controlled by random assignment. As a result, descriptive results can characterize scores recorded in the registry but cannot, on their own, isolate the effect of treatment from other explanations. The absence of reported results further limits what can be concluded from this record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All participants with data available for this outcome measure at all visits.

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: Baseline measures were based on all enrolled participants who received treatment.

6. Primary Endpoint

The registry lists the primary outcome as Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) Total Score, measured over 4-6 weeks after treatment 3 (Up to 104.3 weeks).

The primary endpoint is the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) total score. It is a continuous measure described as a score on a scale, with the primary summary specified as a mean and dispersion specified as a standard deviation. The registry places the assessment 4-6 weeks after treatment 3, within a timeframe listed as up to 104.3 weeks.

TWSTRS combines three subscales: Severity, Disability, and Pain. Each subscale is scored independently, and their total forms the TWSTRS total score. The total ranges from 0, meaning least symptoms, to 85, meaning worst symptoms. A higher score indicates greater symptom severity. Combining symptom severity, functional impact, and pain makes the score a broad measure of the impact of cervical dystonia on patients.

A mean can describe the central level of scores in the participants included in the outcome population. The standard deviation describes how dispersed individual scores are around that mean; it is not a measure of uncertainty in the mean. Both are useful to understand a continuous outcome, but neither can be interpreted without the recorded values and the number of participants contributing data.

The registry identifies the relevant outcome population as participants with data available at all visits. It does not report the mean, standard deviation, participant count for this endpoint, or a baseline-to-follow-up contrast. The endpoint definition explains what would be measured, but the record alone does not show the measured result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary outcome summarized by a mean and standard deviation. General explanation: a continuous measure can take values across a scale, rather than being limited to categories such as yes or no. For TWSTRS, a mean gives the average score among participants whose data are included in the analysis. The standard deviation describes the spread of individual scores around that mean. A larger standard deviation indicates more variation in scores, not necessarily greater uncertainty about the mean.

The TWSTRS score has a defined direction: higher values indicate greater symptom severity. Its total combines Severity, Disability, and Pain subscales, with a range from 0 to 85. This direction makes interpretation of a reported score possible in principle. However, a scale definition does not reveal where participants' scores fell, and no mean or standard deviation is reported in the registry record.

General explanation: an effect estimate is a numerical description of a comparison or change, such as a difference between two means or a change from an earlier measurement. Its interpretation depends on the comparison being made, the people included, and the assumptions behind the analysis. This registry record does not report a primary effect estimate or specify a comparison for the primary outcome. It is therefore not possible to infer an effect from the endpoint definition alone.

A confidence interval is a range generated by a statistical procedure to represent uncertainty around an estimate. Its width depends on factors such as the variability of observations and the information available to the analysis. A confidence interval does not automatically account for bias, confounding, or missing data. No confidence interval for the primary outcome is reported in the registry record, so its precision cannot be assessed.

A p-value, when reported, is a measure tied to a statistical test and its null hypothesis; it is not the probability that a treatment works or that the null hypothesis is true. The registry lists zero analyses and does not report a primary-outcome p-value. No significance conclusion can be drawn from the record.

The sample-size assumptions describe planning illustrations, not the study's own design justification. The illustrations are described as using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. They consider detecting a stated fraction of the observed effect. For time-to-event tables, the stated quantity is total events; for other tables, it is participants per arm. These assumptions explain how planning quantities are framed, but they do not mean that the registry was randomized, that the allocation was equal in practice, or that a particular power was observed. Sample sizes from such calculations are planning illustrations, never observed power. The registry record does not report its own sample-size justification.

General explanation: planning sample sizes depend on the effect considered important or expected, the variability or event rate, the significance threshold, and the desired power. A calculation based on an observed effect can be useful as a hypothetical planning exercise, but it should not be mistaken for an analysis of the original registry. Since the registry record does not give a numerical primary effect, it does not allow the planning assumptions alone to be used to reconstruct the primary finding.

The observational design is important for statistical interpretation. Random assignment, when used, can help balance measured and unmeasured factors between groups on average. This registry instead observed treatment prescribed in routine clinical practice. Physician decisions and participant characteristics were not assigned by the study according to the record. Statistical adjustment could sometimes address measured differences, but the registry record lists no analyses and does not describe an adjustment strategy. It is not appropriate to assume that adjustment was performed.

The outcome population includes participants with data available for the measure at all visits. General explanation: restricting analysis to participants with complete measurements can make an estimate less representative if the availability of data is related to scores, health, or treatment. Other approaches to missing data require assumptions and methods that should be stated. The registry record does not report the number with complete outcome data or a method for handling missing measurements, so the consequences cannot be assessed.

Finally, multiple outcomes can raise a multiplicity issue: when many hypotheses are tested, the chance of at least one nominally significant finding can increase. General statistical practice may address this through prespecified primary outcomes, adjusted thresholds, or a clear distinction between confirmatory and exploratory analyses. The registry lists a primary outcome and secondary outcomes, but does not report whether any multiplicity adjustment was planned or performed. With no analysis results, there are no reported tests to interpret.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("BOTOX®")
n   <- c(479)
m   <- c(27.1)
sp  <- c(14.6)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  BOTOX®  479  27.100  14.600  25.789  28.411

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and lists secondary outcomes concerning mild cervical dystonia severity, clinician global impression of change, patient global impression of change, and pain numeric rating scale score. Across the record, five outcome measures are listed. Having several outcomes can create multiplicity concerns if multiple statistical tests are conducted, because the chance of at least one apparently notable result may rise. General statistical practice is to specify which outcome is primary and whether secondary analyses are confirmatory or exploratory, and to state any adjustment strategy. The registry record does not report whether a multiplicity adjustment was planned or used.

The record lists zero analyses. It therefore provides no estimates or test results across which multiplicity could be evaluated. Statistical procedures for handling multiple comparisons are not reported in the registry record.

The primary outcome population is described as all participants with data available for the outcome at all visits. This definition indicates that data availability affects inclusion in the endpoint analysis. The record does not report the number of participants with complete data, the pattern or reasons for missing measurements, or a method for handling missing data. It is not possible to assess whether participants with complete observations differed from those without them, or how missingness may have affected an estimate.

The registry also does not report a primary analysis population beyond the outcome-specific description, an intention-to-treat approach, or an alternative analysis population. These details matter because the participants included in an analysis determine the population to which its result applies. The record does not give outcome denominators or a statistical plan specifying how the listed outcomes would be analyzed.

Thus, both multiplicity handling and missing-data handling are not reported in the registry record. No adjustment or imputation method should be assumed.

12. 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: cardiac arrest (0.3%), dysphagia (0.2%), chest pain (0.2%), pyrexia (0.2%), urinary tract infection (0.2%).

For the BOTOX® group, the registry reports 1041 at risk for serious adverse events and 33 affected. It separately reports 1041 at risk for other adverse events and 138 affected. These are the counts as recorded; they should not be combined or converted into rates without a defined denominator and analysis approach. The record does not explain whether the same participants could contribute to both categories.

The registry lists serious adverse event terms with percentages: Cardiac arrest, 0.3%; Dysphagia, 0.2%; Chest pain, 0.2%; Pyrexia, 0.2%; Urinary tract infection, 0.2%; and Hip fracture, 0.2%. The denominator and method used for these term percentages are not reported in the registry record. The listed terms should therefore be read as registry safety entries, not as evidence about comparative risk.

Deaths are not reported in the registry record. The adverse-event counts do not by themselves establish that an event was caused by treatment. Because this was observational care, and the record does not provide a control comparison or causal analysis, the figures describe reported events rather than treatment-attributable effects. They also do not provide a full account of event timing, duration, or outcomes.

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

The registry record is useful for defining the clinical setting and the outcome of interest. It describes an observational study of onabotulinumtoxinA use for cervical dystonia, with treatment prescribed as standard care. It identifies TWSTRS total score as the primary endpoint and explains that higher scores indicate greater symptom severity. It also records safety counts and selected serious adverse-event terms.

Those descriptions do not establish what happened to participants' TWSTRS scores. The record does not report the primary mean, standard deviation, a change estimate, confidence interval, or test result. It also lists zero analyses. Without numerical outcome findings, the direction and precision of the primary outcome cannot be evaluated from this record.

Even if descriptive outcome estimates were available, the design would not by itself support a causal treatment conclusion. Care was not assigned by the study, and the record states that allocation is not stated and the arms are not a like-for-like control comparison. An observed score pattern in an observational registry may reflect treatment, participant characteristics, clinical decisions, or other influences. The record gives no analysis that separates these explanations.

The safety counts should also be interpreted descriptively. They report affected counts and listed event terms, but the record does not establish causation or provide comparative risk estimates. The percentages accompanying serious event terms have no reported denominator or calculation method in the record.

Thus, the registry record can establish what was intended to be measured and what safety entries were recorded, but it cannot support a numerical conclusion about the primary outcome, a claim of efficacy, or a causal safety conclusion. Missing outcome results are not evidence of either benefit or lack of benefit; they leave the treatment effect unquantified in this record.

14. Why This Trial Matters Statistically

CD-PROBE illustrates an important distinction between a registered clinical study and a reported statistical result. The record supplies a clearly defined primary measure, its scale direction, an assessment timeframe, and an outcome population description. These elements help readers understand what the study intended to characterize. But without a reported mean, dispersion, or analysis, the endpoint definition cannot answer the clinical question on its own.

The observational context is also statistically important. Treatment in routine care can be studied to describe how outcomes are recorded in practice, but it does not create the controlled conditions of randomized assignment. If comparative findings are reported, interpretation requires attention to how groups came to receive their care and whether important differences were addressed. This record explicitly cautions that the arms are not a like-for-like control comparison.

The registry further highlights why outcome populations and missingness need transparent reporting. The primary outcome is defined for participants with data available at all visits, but the number contributing data and the missing-data approach are not reported. Readers therefore cannot determine how much information underlies the endpoint or whether the analyzed participants represent the enrolled registry population.

Finally, the registry includes several outcomes and safety entries but reports zero analyses. Without analysis results and details of multiplicity handling, there is no statistical basis for judging the size, precision, or robustness of an outcome finding. This is a useful reminder that registration details, safety counts, and planning calculations are not substitutes for transparent outcome reporting. The record describes the study framework, while leaving the primary statistical result unreported.

15. 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.

A key limitation is the absence of numerical primary-outcome results. Although the registry defines TWSTRS total score, the mean and standard deviation are not reported. The record also does not give a change from an earlier assessment, a confidence interval, or a test result. It lists zero analyses, so no statistical estimate can be assessed for magnitude or precision.

The outcome population is limited to participants with data available at all visits, but the record does not state how many participants met that condition. It does not report missing-data patterns, reasons for unavailable measurements, or methods used to address missingness. The effect of this restriction on representativeness cannot be assessed.

The design is observational, with BOTOX® received as standard care under physician prescription and no study intervention administered. Allocation is not stated, and the record cautions that the arms are not a like-for-like control comparison. These features limit causal interpretation, even apart from the absent outcome estimates. The registry record does not describe statistical adjustment for differences between participants or groups.

The record lists multiple outcome measures, but it does not report a statistical plan or whether multiplicity was addressed. It also does not report its own sample-size justification, interim analyses, or the analysis populations beyond the primary outcome population description. These omissions make it difficult to evaluate how analyses were planned or how conclusions would have been selected.

For safety, the registry provides affected counts and selected serious event terms, but does not report the denominator or method underlying the listed term percentages. Deaths are not reported in the registry record. Event timing, attribution, and a comparative safety analysis are not established by the listed counts. Together, these limitations mean the record describes study structure and selected safety observations but does not provide a basis for estimating treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: CD-PROBE: Cervical Dystonia Patient Registry for the Observation of onabotulinumtoxinA Efficacy — NCT00836017.
• Registry record last updated 2014-07-17; status last verified 2014-06.
• Results first posted 2014-07-17.
• 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.

19. Record Summary

CD-PROBE (NCT00836017) is a completed observational registry sponsored by Allergan concerning onabotulinumtoxinA use in cervical dystonia. The record lists enrollment of 1046, with a study start of 2009-01 and primary completion of 2013-08. Participants received BOTOX® as standard care prescribed by physicians; no intervention was administered as part of the study.

The primary outcome is mean TWSTRS total score 4-6 weeks after treatment 3, with the timeframe listed as up to 104.3 weeks. The outcome population is participants with data available at all visits. The record lists five outcome measures and zero analyses, and does not report numerical primary-outcome results. It also lists adverse-event counts and serious event terms, without establishing causation. The observational design and absence of a like-for-like control comparison limit causal interpretation.