Cognitive Behavioural Therapy Software for the Treatment of Depression in People With Multiple Sclerosis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Cognitive Behavioural Therapy Software for the Treatment of Depression in People With Multiple Sclerosis (NCT00678496), a randomized na study. The primary outcome is Change in Self-reported Symptoms of Depression, as Measured by Total BDI-II Score.

2. Clinical Question

The clinical question is about whether a randomized comparison of computerised therapy with usual care could be conducted in people with multiple sclerosis and depression, and about obtaining preliminary estimates to inform a definitive trial. The stated aim was not limited to estimating an effect: recruitment rate and other trial-design parameters were also objectives. The record describes a parallel-group randomized trial with enrollment of 24 and lists CBT software and treatment as usual as the interventions. It also identifies change in disease-specific quality of life, measured using the MSIS-29, as a secondary outcome. Because no outcome analysis is reported in the registry record, this information does not establish the size or direction of any difference between the groups.

3. Trial Design

This was a randomized, parallel-group pilot study sponsored by the University of Sheffield. The registry lists the trial as completed and gives enrollment of 24. The intervention descriptions list CBT software and treatment as usual. The arm descriptions allocate 12 participants to CBT software delivered at home or in a primary care facility and 12 to treatment as usual. These are the registry’s arm figures; they do not establish how many participants contributed data to each outcome analysis.

The record states that masking was none. It does not report further details about sequence generation, concealment of allocation, or the practical procedures used when assigning participants. The registered trial dates are start in 2008-10 and primary completion on 2010-01-31. The record describes a 3 month follow-up objective, while the listed primary outcome is change from baseline at 21 weeks. How these timing details relate to each planned assessment is not further explained in the registry record.

The stated purpose was to test whether a randomized controlled trial of computerised cognitive behavioural therapy for depression in people with multiple sclerosis was feasible. The objectives included identifying a realistic patient recruitment rate and obtaining estimates of parameters needed to design a definitive trial, including its sample size. Preliminary information about depression and quality of life was also intended. The trial therefore had a pilot and feasibility role, rather than being described in the registry as a definitive test of effectiveness.

Participants were to be assessed as experiencing clinical levels of depression and recruited from two participating MS Centres. The record does not report details such as the number screened, reasons for non-participation, adherence to the software, or the care received in the usual-care group. It also does not report a protocol description beyond the stated objectives and registered outcomes. The study is listed as completed, but completion status alone does not indicate that all planned assessments were obtained or analyzed.

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: Participants were invited to take part via clinic mailouts. Responders were excluded if their Beck Depression Inventory score was too high, too low, if they were under the care of a psychiatrist, or were not resident within the boundaries of participating primary care trusts (UK NHS commissioning bodies 2001-2013), or if they refused consent.

Overall Study

Analysis population for the primary outcome, as defined in the registry: There may be different numbers of patients analysed at 8 weeks and 21 weeks, as patients may have dropped out, or there may have been missing information at 8 weeks meaning that the score could not be calculated, but the patient was still followed up at 21 weeks.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

6. Primary Endpoint

The registry lists the primary outcome as Change in Self-reported Symptoms of Depression, as Measured by Total BDI-II Score, measured over 21 weeks.

The primary outcome is change from baseline in self-reported symptoms of depression, measured by total score on the Beck Depression Inventory II, at 21 weeks. The BDI-II contains 21 items. Each item is rated on a 4-point scale ranging from 0 to 3, and the total is formed by summing the item ratings. The maximum total score is 63, described in the record as severe depression. The endpoint is expressed in units on a scale, and the registered summary measure is a mean with standard deviation.

A change score describes how a participant’s measurement differs from their own baseline measurement. In general, using change from baseline can make the outcome’s interpretation explicitly relative to the starting assessment. The between-group comparison would then concern the average change in the intervention group relative to the average change in the usual-care group. The registry record does not provide those group averages or a comparative estimate, so the direction and magnitude of any difference cannot be described.

The BDI-II is used as a self-report measure of the severity of depressive symptoms, not as a direct measure of every aspect of depression or multiple sclerosis. A scale score can capture reported symptoms in a structured way, while remaining dependent on participants’ responses and on availability of the items needed to calculate a total. The record notes that missing information could prevent calculation of a score at an assessment. The clinical interpretation of a change also depends on the scale, the population, and the quality of the comparison; a numerical change alone is not reported in this registry record.

The secondary outcome is change in disease-specific quality of life measured with the 29-item Multiple Sclerosis Impact Scale. The registry does not provide a result for that outcome either. It does not report the scoring details or a threshold for interpreting change on the MSIS-29.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the registered summary measure mean?

The primary outcome is continuous: it is a score on a scale, and the registry specifies a mean and standard deviation as the summary statistics. In general, a mean describes the central level of measured values, while a standard deviation describes how spread out participant values are around that mean. They answer different questions. A group mean summarizes the average score or change; the standard deviation describes variation among individual observations. Neither summary alone establishes the difference between randomized groups.

The registered outcome is change from baseline at 21 weeks. A change score is calculated for each participant from their baseline and follow-up measurements, and group summaries can then describe average change. A comparative analysis would need to specify how those changes are contrasted and how uncertainty is estimated. The registry does not report the observed means, standard deviations, analysis method, or comparative estimate. It therefore does not permit a reconstruction of the primary comparison from the registry record.

In general, randomization supports a comparison between assigned groups by reducing systematic differences in expectation, but it does not guarantee that all baseline characteristics will be identical in a small study. The record identifies the study as randomized and parallel, but does not describe the randomization procedure or report baseline characteristics. No claim about balance between the groups can be made from these registry entries alone. Masking is recorded as none; the record does not specify who knew the assigned treatment or how outcome assessment was conducted.

What does uncertainty mean?

In general, an estimate is more informative when accompanied by a measure of uncertainty, such as a confidence interval. A confidence interval reflects both the observed data and the assumptions of the method used to analyze them. It helps readers judge which effect sizes remain reasonably compatible with the data. It does not guarantee that the true effect lies within a particular interval, and its interpretation relies on the statistical procedure and study design. Since no effect estimate or interval is reported for the primary outcome, the precision of the comparison cannot be judged.

A test statistic and p-value are also analysis outputs, not descriptions of clinical importance. In general, a p-value measures how unusual the observed data, or data more extreme, would be under a specified null model and test procedure. It does not give the probability that the null hypothesis is true, and a value alone does not show whether a difference is large enough to matter. The registry does not report a primary-outcome p-value or identify a testing procedure. The absence of a reported analysis should not be treated as a non-significant finding.

Why can over-dispersion matter?

In general, over-dispersion means that observed variability is greater than a statistical model allows for. A model that understates variability can produce uncertainty estimates that are too small, making results appear more precise than they are. This concern depends on the type of outcome and the model used. The registered primary outcome is a continuous scale measure summarized by a mean and standard deviation, and no outcome model is specified in the record. There is no basis to say that over-dispersion was assessed or affected an analysis in this trial.

How should the planning assumptions be read?

The registry describes sample-size planning as an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation. It says the effect to detect is a stated fraction of the observed effect. These are planning assumptions, not a report of the trial’s original design rationale. In general, a sample-size calculation estimates the amount of information needed to detect a target effect under chosen assumptions; changing the assumed effect or variability changes the planning result. The registry does not report the protocol’s sample-size justification or a formal statistical plan. The numerical results of the planning illustration are not reported in the registry record. Such calculations should not be described as observed power.

What can be inferred from the registered design?

The randomized parallel design identifies a planned comparison of two groups, but the registry’s design description is not itself an analysis. A valid interpretation of an outcome comparison depends on the endpoint definition, analysis population, missing-data handling, and chosen statistical method, among other details. The record does not report whether the primary analysis followed assignment, used a particular adjusted or unadjusted model, or included sensitivity analyses. It also does not report an analysis population or the number analyzed for the primary outcome. Those omissions prevent a statistical reader from checking the analysis assumptions or reproducing its result.

The registry reports a continuous primary measure and a continuous quality-of-life outcome, but does not give their outcome distributions or analysis outputs. General methods such as comparing group means, modeling change, or adjusting for baseline can address different analytic questions and rely on different assumptions. None should be attributed to this trial without a record of the method used. The trial’s pilot purpose and small recorded enrollment also make it especially important not to equate a planning objective with evidence about a definitive treatment effect.

10. Multiplicity, Missing Data and Analysis Populations

The record lists two outcome measures: change in BDI-II total score as the primary outcome and change in MSIS-29 as a secondary outcome. It does not report a statistical plan specifying how these outcomes were to be tested, whether one was designated as the sole confirmatory comparison, or how multiplicity was to be handled. When multiple outcomes or time points are examined, the chance of at least one apparently unusual result can increase. In general, researchers may address this through prespecification, adjustment, or a clear distinction between primary and exploratory analyses. The registry does not say which approach, if any, was used.

The primary outcome is identified at 21 weeks. The record also refers to possible differences in the numbers analyzed at 8 weeks and 21 weeks, and the trial description mentions a 3 month follow-up objective. It does not fully map all outcome time points or explain which comparisons were planned at each assessment. The registry flags that the primary outcome has several categories or time points and is not reduced to one comparison. The specific categories or comparisons behind that flag are not reported in the registry record.

Missing-data handling is also not reported. The registry notes that participants could drop out or have missing information at 8 weeks that prevents calculation of a score, while still being followed up at 21 weeks. This makes clear that the numbers with usable measurements may vary by assessment. It does not give the observed missingness, reasons by group, or methods used to account for missing outcomes. In general, missingness can affect both the precision and the validity of an estimate, particularly if the likelihood of a missing value is related to participant characteristics or outcomes.

The record does not identify an intention-to-treat population, a per-protocol population, or any other analysis population. It therefore does not establish whether participants were analyzed according to randomized assignment or according to treatment received. Nor does it report sensitivity analyses examining alternative assumptions about missing data. These details are important for judging how robust a comparison might be; they are not available in the registry record.

11. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Serious events with the highest arm-level rate: broken arm (12.5%).

The adverse-event record lists serious adverse events separately for the two groups. In the CCBT group, 8 participants were at risk for serious adverse events and 1 was affected; the listed serious term was “Broken arm,” reported as 12.5%. In the treatment-as-usual group, 10 participants were at risk and 0 were affected. The record reports no deaths in either group. It also records 0 other adverse events among 8 participants at risk in the CCBT group and 0 among 10 at risk in the usual-care group.

These are descriptive safety counts, not a statistical comparison. The at-risk figures are the denominators recorded for these adverse-event summaries and should not be assumed to equal the number enrolled or the number analyzed for the depression outcome. The registry does not report a method for comparing safety between groups, uncertainty intervals, the timing of the event, or further clinical details about the broken arm. The listed term does not establish its cause or whether it was related to treatment.

In general, the absence of a reported event in a group does not establish that the risk is zero. Small numbers and limited follow-up can leave substantial uncertainty about uncommon events. These registry figures describe what was recorded, but they do not support a broad conclusion about comparative safety.

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

This record describes a pilot trial designed to compare computerised cognitive behavioural therapy with treatment as usual for depression in people with multiple sclerosis. It states that the primary outcome was change in BDI-II score at 21 weeks and that quality of life measured by the MSIS-29 was a secondary outcome. It also records the trial’s feasibility objectives, including learning about recruitment and estimating parameters for a definitive trial.

The record does not provide the outcome analysis. It gives no group-level primary outcome results, comparative estimate, confidence interval, or p-value, and no analysis is listed. As a result, it cannot show from the posted data whether the intervention group’s average change differed from the usual-care group, or how precise a difference might be. This absence of a reported result is not evidence that the groups were the same, nor is it evidence that they differed.

The enrollment and arm descriptions give information about the trial’s planned and recorded group structure, not about the amount of usable follow-up data for each endpoint. The record explicitly notes that the number analyzed could vary across assessments because of dropout or missing information. Without outcome-specific analysis counts and missing-data details, the extent to which the primary comparison reflects all randomized participants is not reported.

The stated pilot objective also limits what can be inferred from the design alone. A pilot can inform the practical conduct and planning of a later study, but its existence does not establish that the intervention is effective or ineffective. The record does not report whether recruitment targets were met, whether the software was used as intended, or whether a definitive trial protocol was completed. Those outcomes are not reported in the registry record.

The appropriate conclusion is therefore narrow: the registry documents a completed randomized pilot with a depression endpoint and a quality-of-life outcome, alongside serious adverse-event summaries. It does not provide the comparative efficacy analysis needed to quantify an effect. The posted information is useful for understanding the intended question and design, but it is insufficient to draw an outcome-based conclusion about treatment effects.

13. Why This Trial Matters Statistically

This trial is statistically relevant because it was explicitly framed as a pilot intended to inform a definitive randomized trial. That purpose connects clinical research with study design: a future trial requires credible estimates of recruitment, outcome variability, follow-up completion, and the effect size worth detecting. The registry lists these as objectives in broad terms, but does not report the resulting estimates. Distinguishing intended learning from reported evidence is central to reading a pilot study responsibly.

The trial also illustrates why participant enrollment is not the same as endpoint information. The registry records enrollment of 24 and describes 12 participants in each arm, while also noting that different numbers may contribute data at 8 and 21 weeks. A planned group size therefore does not automatically tell a reader the effective sample size for a particular outcome analysis. Assessment-specific completion and the analysis population matter for interpreting precision.

The primary outcome is a participant-reported scale score. Such measures can provide a structured way to assess symptoms, but statistical interpretation depends on how the score is summarized, how baseline and follow-up are handled, and how missing responses affect score calculation. The registry defines the BDI-II scoring structure and the 21-week change endpoint, but does not report the comparative analysis. This makes the distinction between endpoint definition and endpoint result especially clear.

Finally, the record includes a planning illustration with stated assumptions but no numerical planning outputs. That distinction matters because sample-size planning is conditional on assumptions and is not a measure of observed power. A pilot’s contribution to a later trial depends on the quality and transparency of the information collected and reported. Here, the design and aims are recorded, while the outcome and planning estimates needed to evaluate those contributions are not reported in the registry record.

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 most important limitation for statistical interpretation is that the registry record does not report an analysis of the primary outcome. There are no group estimates, treatment contrast, uncertainty interval, or test result. The secondary quality-of-life outcome also has no reported result. The study’s completed status therefore cannot be taken as evidence that outcome data were analyzed or that a particular conclusion was reached.

The record does not report the number of participants with evaluable BDI-II data at 21 weeks or the analysis population. It notes the possibility of dropout and missing information, including the possibility that missing information at 8 weeks could prevent score calculation even if a participant was followed at 21 weeks. However, observed missingness, reasons for missingness, and the methods used to handle missing values are not reported. This leaves uncertainty about the available outcome information and the potential influence of missing data.

Further details needed to assess the analysis are also absent. The statistical method, any baseline adjustment, model assumptions, handling of multiple outcomes or assessment times, and sensitivity analyses are not reported in the registry record. Randomization is recorded, but the sequence-generation and allocation procedures are not described. Masking is recorded as none, without additional information about outcome assessment.

The record’s pilot purpose and the enrollment and arm descriptions should be read in that context. It does not report recruitment performance, adherence to CBT software, the components of treatment as usual, or the recruitment flow. The planning illustration is described by assumptions, but its numerical output is not reported. These limitations prevent independent assessment of the primary treatment comparison and of the study’s contribution to planning a definitive trial.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Cognitive Behavioural Therapy Software for the Treatment of Depression in People With Multiple Sclerosis — NCT00678496.
• Registry record last updated 2021-03-17; status last verified 2020-09.
• Results first posted 2021-03-17.
• 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.

18. Record Summary

This completed, randomized parallel-group pilot was sponsored by the University of Sheffield. The registry records enrollment of 24, with 12 assigned to CBT software and 12 to treatment as usual in the arm descriptions. The intervention could be delivered at home or in a primary care facility, and masking was listed as none.

The primary outcome was change from baseline in BDI-II total score at 21 weeks. Change in MSIS-29 was listed as a secondary outcome. The stated purpose was to assess feasibility and obtain estimates useful for designing a definitive trial. The registry does not report an outcome analysis, the numbers analyzed for the primary endpoint, or the statistical methods used. Serious adverse-event summaries include a broken arm in the CCBT group and no serious events in the usual-care group; no deaths were recorded.