Effectiveness of Vitamin Supplementation in Treating People With Residual Symptoms of Schizophrenia: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness of Vitamin Supplementation in Treating People With Residual Symptoms of Schizophrenia (NCT00611806), a randomized phase 4 study. The primary outcome is Positive and Negative Syndrome Scale (PANSS).

2. Clinical Question

The study’s stated aim was to evaluate folate and B12 supplementation in relation to negative symptoms in people with schizophrenia. The posted primary outcome, however, is the Positive and Negative Syndrome Scale (PANSS), which includes positive symptoms, negative symptoms, and general psychopathology. Its reported change therefore concerns a broader symptom measure than negative symptoms alone.

The arm summaries report a mean change per week of -0.21 for folate with B12 and -0.22 for placebo. Their respective 95% confidence intervals are -0.35 to -0.07 and -0.42 to -0.03. The registry record does not report a two-arm comparison for this continuous outcome. Accordingly, these arm-specific summaries describe the posted results, but do not establish a treatment-versus-placebo difference or its statistical uncertainty.

3. Trial Design

This was a phase 4, randomized, parallel-group trial with quadruple masking. The registry lists Massachusetts General Hospital as the sponsor and schizophrenia as the condition. Enrollment was 140. The study was listed as completed, with a start date of 2007-12 and a primary completion date of 2010-08.

Participants were assigned to folate with B12 or placebo. Both regimens were described as lasting 18 weeks. The primary outcome timeframe is labeled baseline versus week 16, so the stated treatment duration and the primary measurement timeframe are not identical. The registry record does not explain the relationship between these timepoints.

The primary measure was change from baseline on PANSS, reported as change in symptoms per week. The analysis population for the posted primary outcome included participants with at least one post-baseline visit (n = 135). The record says 120 participants completed to the week 16 endpoint and that 15 did not complete the entire 16 weeks but did complete at least one post-baseline visit with a PANSS assessment. The reason for the difference between these analysis counts and the enrollment figure is not reported in the registry record.

Five secondary outcomes are listed. They cover cognitive performance measured with the MATRICS Cognitive Battery Composite Score; positive and negative symptom measures using PANSS and SANS; associations with several genotypes; and relationships between symptom response and changes in biological measurements. The record lists six outcome measures overall and zero analyses. Allocation details beyond “randomized,” the sequence-generation method, concealment procedures, and the specific masking roles 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.

Before assignment: 189 Participants were screened for enrollment, but 49 were excluded. 40 were ineligible, 2 withdrew consent, 1 terminated because of an adverse event, and 6 were terminated because of study visit noncompliance.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Participants analyzed were those who completed at least 1 post-baseline visit or more (n = 135). 120 participants completed the study to the week 16 endpoint; however, 15 participants did not complete the entire 16 weeks, but completed at least one post-baseline study visit where the PANSS assessment was performed.

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 Positive and Negative Syndrome Scale (PANSS), measured over Baseline vs. Week 16.

The primary outcome is change from baseline on PANSS, expressed as symptoms changed per week. PANSS includes three subscales: positive symptoms, negative symptoms, and general psychopathology. The description gives score ranges of 7-49 for each of the positive and negative subscales, and 16-112 for general psychopathology. Items are rated on a scale of 1-7, and scores are formed by adding the relevant items.

The registry’s interpretation is that a negative reported score represents a decrease in total PANSS score per week relative to baseline, while a positive score represents an increase. The arm means are both negative: -0.21 for folate with B12 and -0.22 for placebo. These are within-arm summaries, not a direct estimate of the difference between assigned groups.

PANSS is used to quantify multiple symptom domains in schizophrenia, which makes it relevant to the trial’s broad symptom assessment. Its scope also matters when interpreting the stated aim of reducing negative symptoms: the posted primary outcome is not limited to the negative subscale. The registry does not report a separate primary result for the negative subscale in the primary-outcome entry. The timeframe is baseline versus week 16, while the intervention description says 18 weeks; further detail about the timing of assessment is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the mean represent?

The primary outcome is continuous, and the reported parameter is the mean. A mean describes the average value in the group analyzed; it does not show the full spread of individual participant outcomes. The posted values are changes per week relative to baseline, not raw PANSS scores at week 16. According to the registry description, a negative value indicates a decrease in total PANSS score per week and a positive value indicates an increase.

The means are reported separately for folate with B12 and placebo. They are -0.21 and -0.22, respectively. The registry also reports a 95% confidence interval for each mean. The intervals are -0.35 to -0.07 for folate with B12 and -0.42 to -0.03 for placebo. No standard deviation or other dispersion measure is posted for this outcome; the stated dispersion is the confidence interval.

What does a confidence interval communicate?

General statistical explanation: a confidence interval is constructed using a statistical procedure intended to capture the underlying parameter at its stated coverage rate over repeated use of that procedure, if its assumptions hold. For a reader, the interval conveys uncertainty about the estimated mean and the range of values consistent with the data and method. It does not mean that there is a 95% probability that the fixed, true mean is inside this particular interval.

The intervals in the registry are for each arm’s mean. A direct randomized comparison would ordinarily require an estimate of the contrast between the groups and its uncertainty. Neither that contrast nor its confidence interval is reported. The registry identifies the two-arm comparison as not estimable for this continuous endpoint. A p-value for the contrast is also not reported in the registry record.

Why does the comparison matter?

Within-arm change and between-arm difference answer different questions. A group’s change from baseline describes how its measured outcome changed over time. A treatment comparison asks whether the change differed between the randomized groups. Change in both groups can occur for many reasons, including factors shared by participants or the study period; the arm-specific means by themselves cannot separate such factors from a treatment contrast. General statistical explanation: randomization is designed to make a comparison between groups informative, but the interpretation still depends on the relevant outcome data and analysis being reported.

Here, the registry displays arm-specific mean changes but no direct analysis of the contrast. It is therefore appropriate to describe the two means and their intervals without converting them into a claim about a difference. The absence of a posted comparison does not establish that the groups were identical; it means the registry record does not report an estimable comparative result.

How should the analysis population be read?

The primary-outcome description says the analyzed participants were those who completed at least one post-baseline visit (n = 135). It also reports that 120 participants completed the study to the week 16 endpoint, while 15 did not complete all 16 weeks but had at least one post-baseline study visit with a PANSS assessment. The arm-specific primary-outcome counts are n = 89 and n = 46. These population descriptions do not explain the precise analysis model or how measurements at different visits contributed to the per-week estimates. Those details are not reported in the registry record.

General statistical explanation: analysis populations matter because participants may have different amounts of follow-up, and the method used to handle missing measurements can affect estimates and uncertainty. A complete-case approach, a model using available repeated measurements, and other approaches can rely on different assumptions. The registry record does not state which approach was used, so none should be attributed to this trial.

What is the role of the planning illustration?

The planning illustration is based on the observed effect and is not the trial’s design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. Such sample-size figures are planning illustrations, not observed power. General statistical explanation: planning calculations describe the size of a future study under specified assumptions. They do not measure the probability that this completed trial found an effect, and they do not replace a reported treatment comparison.

The registry record does not report the trial’s own sample-size justification, target effect, or statistical analysis plan. Nor does it report details of any interim analyses. Those omissions limit assessment of whether the posted analysis matches the intended design.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists five secondary outcomes and six outcome measures overall. The secondary outcomes address cognitive deficits, positive and negative symptoms, associations with several genotypes, and relationships between symptoms and changes in biological measurements. The record lists zero analyses, and it does not identify a multiplicity-adjustment method. Any adjustment for multiple outcomes or comparisons is not reported in the registry record.

General statistical explanation: when many outcomes or comparisons are examined, the chance of at least one apparently notable result can increase if each is assessed independently without accounting for multiplicity. Whether that issue affects interpretation depends on which analyses were prespecified and how they were conducted. The registry record does not report enough detail to determine the intended hierarchy or analysis plan for the listed outcomes.

For the primary outcome, the record describes an analysis population of participants with at least one post-baseline visit (n = 135). It also says 120 completed to the week 16 endpoint and 15 did not complete the entire 16 weeks but had at least one post-baseline PANSS assessment. The record does not give reasons for incomplete follow-up, arm-specific endpoint completion, or a detailed missing-data method. The handling of missing measurements is not reported in the registry record.

The primary-outcome arm counts are n = 89 and n = 46. The safety denominators are different, and the registry does not explain the difference. The analysis population cannot be assumed to be all randomized participants, nor can it be classified as a particular named analysis set based on the record alone. The randomization sequence, allocation concealment, prespecified analysis population, and protocol-level statistical methods are not reported in the registry record.

11. 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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hospitalization due to worsening psychosis (2.2%), body numbness (2.2%), vision decreased (2.2%), brain tumor (2.2%), cholelithiasis (1.1%).

The registry reports serious adverse event counts among 94 participants at risk in the folate-with-B12 group and 46 at risk in the placebo group. Four participants are listed as affected in each group. These are counts, not a direct comparison adjusted for the different denominators or duration of observation. The registry record does not provide a comparative statistical analysis of serious adverse events.

For other adverse events, 21 participants are listed as affected among 94 at risk in the folate-with-B12 group, and 16 among 46 at risk in the placebo group. These counts should be kept distinct from the serious adverse event counts. The reason the safety group sizes differ from the primary-outcome group sizes is not reported in the registry record.

The listed serious event terms include hospitalization due to worsening psychosis, body numbness, vision decreased, brain tumor, cholelithiasis, and suicidal tendency. The associated percentages are 2.2% for the first four listed terms and 1.1% for the latter two. The registry record does not state which arm each term occurred in within this listing. Death counts are not reported in the registry record.

General statistical explanation: adverse-event counts describe events observed and recorded under the study’s reporting definitions. They do not by themselves establish that an event was caused by an intervention or demonstrate a difference in risk between groups. The record does not provide enough detail to infer causation or to make an adjusted safety comparison.

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

The registry reports mean PANSS change per week relative to baseline in each randomized arm. The mean was -0.21 for folate with B12 and -0.22 for placebo. The corresponding 95% confidence intervals were -0.35 to -0.07 and -0.42 to -0.03. Under the registry’s stated direction, negative scores represent decreases in total PANSS score per week.

These results do not answer whether the mean change differed between the groups. The registry record does not report an estimable two-arm comparison, a contrast confidence interval, or a p-value. A difference should not be inferred by comparing the arm means informally. In particular, the posted intervals describe each arm’s mean rather than the treatment contrast.

The outcome also does not isolate negative symptoms. Although the study’s stated aim concerns reducing negative symptoms, the primary PANSS measure includes positive symptoms, negative symptoms, and general psychopathology. The record lists separate secondary symptom measures, including SANS and the PANSS positive subscale, but does not provide their results in the information reported for this primary endpoint.

The analyzed participants were those with at least one post-baseline visit, and the reported group sizes were n = 89 and n = 46. The record notes that 120 participants completed to week 16 and that 15 others had at least one post-baseline PANSS assessment without completing the full 16 weeks. It does not detail the analysis model or handling of missing observations, which limits evaluation of how these data contributed to the reported means.

General statistical explanation: a randomized design supports a comparison when outcomes are analyzed and reported in a way that preserves the intended comparison. Here, the design is randomized, but the registry’s posted primary result is arm-specific. It therefore documents symptom-change summaries, not a definitive estimate of the effect of assignment to folate with B12 compared with placebo. No conclusion about whether the intervention works or does not work follows from these posted summaries alone.

13. Why This Trial Matters Statistically

This trial illustrates why the distinction between within-group change and a randomized between-group comparison is central to clinical-trial interpretation. Each arm has a reported mean change and confidence interval, but the registry does not provide the direct contrast. The arm summaries can be described precisely, yet they cannot by themselves answer the comparative question that motivates a randomized trial.

It also highlights the importance of defining the outcome carefully. The study’s stated aim concerns negative symptoms, while the primary outcome is PANSS, which includes positive symptoms, negative symptoms, and general psychopathology. A composite or broad-scale result should not be presented as if it were limited to a single symptom domain. The record’s listed secondary measures reinforce that symptom domains and cognitive outcomes were assessed separately.

The analysis population is another important statistical detail. Enrollment was 140, while the primary-outcome description refers to participants with at least one post-baseline visit and reports different group counts. It also distinguishes participants who completed to the week 16 endpoint from those with some post-baseline follow-up. When the analysis population and missing-data method are not fully described, readers cannot determine how incomplete follow-up affected the estimates.

Finally, the registry’s listed secondary outcomes and absence of reported analyses make it difficult to assess the full analysis plan or multiplicity handling. These are not reasons to substitute speculation for results; they are reasons to keep interpretation close to the information recorded. The trial is statistically instructive because a randomized label, arm-level estimates, and confidence intervals do not eliminate the need for a reported comparative analysis, clearly defined populations, and transparent methods.

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 primary limitation for interpreting efficacy is the lack of a reported two-arm analysis for the continuous PANSS outcome. The registry gives an arm-specific mean and confidence interval for each group, but no treatment contrast, contrast confidence interval, or p-value. The registry identifies the comparison as not estimable.

The primary outcome is described as change per week, with a baseline-to-week-16 timeframe, while the intervention descriptions state an 18-week regimen. How these timepoints relate is not reported in the registry record. The detailed statistical model used to estimate change per week is also not reported.

The primary-outcome population is described as participants with at least one post-baseline visit. The record reports 120 participants completing to week 16 and 15 others with at least one post-baseline assessment, alongside arm-specific analysis counts of n = 89 and n = 46. Reasons for incomplete follow-up, arm-specific completion details, and the method for handling missing outcome data are not reported in the registry record.

The record lists five secondary outcomes but reports zero analyses. The status of those outcomes, any prespecified outcome hierarchy, and multiplicity procedures are not reported in the registry record. The sample-size justification and trial statistical analysis plan are also not reported.

For safety, serious adverse events are reported as counts among at-risk groups, but no comparative analysis or causal assessment is provided. The event-term percentages are not assigned to specific arms in the listing. Death counts are not reported in the registry record. These limitations restrict how far the posted results can be interpreted beyond their descriptive content.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Effectiveness of Vitamin Supplementation in Treating People With Residual Symptoms of Schizophrenia — NCT00611806.
• Registry record last updated 2014-08-19; status last verified 2014-07.
• Results first posted 2014-08-19.
• 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

NCT00611806 is a completed phase 4, randomized, quadruple-masked, parallel-group trial sponsored by Massachusetts General Hospital. It enrolled 140 participants with schizophrenia and compared folate with B12 against placebo; both regimens were described as lasting 18 weeks.

The primary outcome was change from baseline on PANSS, reported as symptoms changed per week, with a baseline-versus-week-16 timeframe. The mean was -0.21 (95% confidence interval -0.35 to -0.07) for folate with B12 and -0.22 (95% confidence interval -0.42 to -0.03) for placebo. The registry does not report an estimable two-arm comparison for this continuous outcome.

The primary-outcome population included participants with at least one post-baseline visit (n = 135); 120 completed to week 16 and 15 others had at least one post-baseline assessment. Five secondary outcomes are listed, and the record lists zero analyses. Details of the statistical plan, multiplicity handling, and missing-data methods are not reported in the registry record.