This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms (NCT03669640), a randomized phase 2 study. The primary outcome is Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03669640 |
| Phase | Phase 2 |
| Condition | Schizophrenia, Schizoaffective Disorder |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 131 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants with schizophrenia or schizoaffective disorder and negative symptoms. The registered enrollment was 131. The primary outcome describes a modified intent-to-treat population comprising randomized participants who received at least one dose of study drug.
Intervention
RO6889450, also named ralmitaront in the study title. Part A evaluated monotherapy, including a 150 mg group. Part B evaluated add-on therapy at low or high doses alongside usual antipsychotic treatment(s); the listed doses were 45 mg, 150 mg, and 300 mg.
Comparator
Dose-matched placebo. Part A compared monotherapy with placebo, while Part B compared add-on treatment groups with placebo added to usual antipsychotic treatment(s).
Primary question
How did BNSS avolition/apathy subscores and total scores change from baseline to Week 12 in the study population? The registry record does not report outcome values or analyses, so it does not establish the direction, size, or precision of any treatment-group difference.
The clinical question concerns negative symptoms, with the Brief Negative Symptom Scale (BNSS) named as the primary measure. The record describes two components: the avolition/apathy subscore and the total score. It gives a baseline-to-Week 12 timeframe, but no arm-specific means, standard deviations, estimated contrasts, confidence intervals, or p-values are reported in the registry record. Consequently, a numerical treatment comparison cannot be interpreted from the posted results.
The study included two distinct treatment settings in its design: monotherapy in Part A and add-on therapy in Part B. In the latter, the active treatment was added to usual antipsychotic treatment(s). Those settings should not automatically be treated as one interchangeable comparison: their treatment context differs, and the registry record does not report a combined analysis that would justify pooling them. It also does not report a treatment-effect estimate for any individual dose or part.
The record identifies multiple secondary outcomes, including clinical global impression ratings, PANSS scores, BNSS total score, and DPAS scores. Their inclusion indicates that the study assessed more than the primary BNSS measures, but the registry record reports no analyses for those outcomes. The central question can therefore be stated from the planned endpoint and study groups, but not answered with an observed efficacy estimate from this record.
3. Trial Design
This was a Phase 2, randomized, quadruple-masked, parallel-group study with placebo control. Its title identifies participants with schizophrenia or schizoaffective disorder and negative symptoms. The registry lists a total enrollment of 131 and names Hoffmann-La Roche as sponsor. The study started on 2018-12-04, had a primary completion date of 2023-03-12, and is marked terminated.
The intervention record lists RO6889450 and placebo. Part A was monotherapy: participants received RO6889450 or dose-matched placebo. Part B was add-on therapy: participants received a low or high dose of RO6889450 or dose-matched placebo in addition to usual antipsychotic treatment(s). The listed adverse-event groups identify Part A placebo and 150 mg groups, and Part B placebo and 45 mg, 150 mg, and 300 mg groups. The record does not provide arm-specific enrollment totals for the efficacy endpoint in the information available for interpretation.
Randomization means that treatment assignment was intended to use a chance-based process, which can help balance measured and unmeasured participant characteristics across groups on average. It does not guarantee balance in any particular trial. The registry record does not report the randomization sequence generation, allocation ratio, blocking, stratification factors, or concealment procedures, so those operational details cannot be assessed.
Quadruple masking indicates that masking was a feature of the registered design, but the registry record does not specify which roles were masked or how masking was maintained. A parallel design assigns participants to a treatment group for comparison rather than describing a crossover between treatments. The record does not report treatment duration beyond the primary endpoint timeframe, adherence, protocol deviations, or the criteria and timing behind the termination status.
The primary outcome is described as BNSS avolition/apathy subscore and total score at baseline and Week 12. The registry record does not report the statistical model, analysis contrast, missing-data method, covariate adjustment, or a sample-size justification. As a result, the design features that are known can be described, but the inferential plan cannot be reconstructed in detail.
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
| Stage | Part A: Monotherapy (Placebo) | Part A: Monotherapy (150 mg) | Part B: Add-on Therapy (Placebo) | Part B: Add-on Therapy (45 mg) | Part B: Add-on Therapy (150 mg) | Part B: Add-on Therapy (300 mg) |
|---|---|---|---|---|---|---|
| STARTED | 15 | 12 | 37 | 5 | 30 | 32 |
| COMPLETED | 10 | 7 | 33 | 5 | 27 | 29 |
| NOT COMPLETED | 5 | 5 | 4 | 0 | 3 | 3 |
Reasons for not completing this period:
| Reason | Part A: Monotherapy (Placebo) | Part A: Monotherapy (150 mg) | Part B: Add-on Therapy (Placebo) | Part B: Add-on Therapy (45 mg) | Part B: Add-on Therapy (150 mg) | Part B: Add-on Therapy (300 mg) |
|---|---|---|---|---|---|---|
| Study Terminated by Sponsor | 0 | 0 | 0 | 0 | 1 | 0 |
| Lost to Follow-up | 0 | 0 | 2 | 0 | 0 | 0 |
| Death | 0 | 0 | 1 | 0 | 0 | 0 |
| Withdrawal by Subject | 1 | 2 | 1 | 0 | 1 | 3 |
| Protocol Violation | 1 | 0 | 0 | 0 | 0 | 0 |
| Physician Decision | 0 | 2 | 0 | 0 | 0 | 0 |
| Disease Relapse | 1 | 0 | 0 | 0 | 0 | 0 |
| Adverse Event | 2 | 1 | 0 | 0 | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The modified intent-to-treat (mITT) population included all randomized participants who received at least one dose of study drug.
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.
Only the first 6 of 7 groups are shown.
| Characteristic | Unit | Part A: Monotherapy (Placebo) | Part A: Monotherapy (150 mg) | Part B: Add-on Therapy (Placebo) | Part B: Add-on Therapy (45 mg) | Part B: Add-on Therapy (150 mg) | Part B: Add-on Therapy (300 mg) |
|---|---|---|---|---|---|---|---|
| Participants analysed | 15 | 12 | 37 | 5 | 30 | 32 | |
| Age, Continuous | Years | 42.7 (SD 9.9) | 43.3 (SD 6.6) | 41.3 (SD 9.7) | 41.6 (SD 11.3) | 40.0 (SD 9.6) | 40.9 (SD 9.2) |
| Sex: Female, Male: Female | Participants | 3 | 3 | 10 | 0 | 11 | 12 |
| Sex: Female, Male: Male | Participants | 12 | 9 | 27 | 5 | 19 | 20 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 | 0 | 2 | 0 | 6 | 5 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 14 | 11 | 35 | 5 | 24 | 27 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 1 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 1 | 0 | 8 | 0 | 6 | 4 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 1 | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 12 | 9 | 11 | 5 | 7 | 10 |
| Race (NIH/OMB): White | Participants | 2 | 3 | 16 | 0 | 16 | 18 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 | 0 | 1 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 1 | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Brief Negative Symptoms Scale (BNSS) Avolition/Apathy Subscore and Total Score at Baseline and Week 12, measured over Baseline to Week 12.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Units on a scale |
| Endpoint classification | Continuous Endpoint |
The primary outcome is the Brief Negative Symptom Scale (BNSS) avolition/apathy subscore and total score from baseline to Week 12. The registry describes the BNSS as a 13-item instrument designed for clinical trials to measure negative symptom severity across five domains. Its items are organized into 6 subscales: anhedonia, distress, asociality, avolition, blunted affect, and alogia. Each item is rated on a 7-point scale from 0 to 6, where 0 means absent symptoms and 6 means severe symptoms.
The total score is calculated by summing the 13 individual items and ranges from 0 to 78. The avolition/apathy subscale contains 2 items and ranges from 0 to 12. These scale definitions help explain what a score represents: higher values correspond to greater symptom severity under the stated scoring description. They do not establish how scores changed in this study, because the registry record does not report baseline or Week 12 values.
Using a defined instrument gives investigators a consistent way to quantify a clinical construct across participants and time points. The avolition/apathy subscore focuses on that domain, while the total score represents the broader set of BNSS items. Examining both can describe a focused symptom domain alongside overall scale severity. These are general measurement considerations; they do not establish the instrument's performance in this particular study.
The endpoint is expressed as a mean with standard deviation, but no outcome means, standard deviations, or treatment contrasts are reported in the registry record. It is therefore not possible to assess the observed change, compare treatment groups, or determine the precision of an estimate for either BNSS measure.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record identifies the endpoint and study design, but it does not provide the numerical primary outcome results. In particular, there are no reported BNSS means or standard deviations at baseline or Week 12, no change estimates, no between-group contrasts, and no confidence intervals or p-values. The record lists 0 analyses. Thus, the posted results do not support a numerical estimate of how RO6889450 groups compared with placebo on the primary outcome.
The primary outcome description includes more than one score and more than one time point. The registry's stated reason for not reducing this outcome to a single comparison is that it has several categories or time points. Without an identified primary contrast, even a set of score values would need careful interpretation: a comparison might concern the avolition/apathy subscore, total score, change over time, or a particular treatment part and dose. The registry record does not supply the analysis needed to resolve those possibilities.
A mean describes the average score in a group, while a standard deviation describes the spread of individual scores around that average. A difference in group means can be an interpretable summary, but its uncertainty depends on the data and analysis. A confidence interval would show a range of values compatible with the estimated contrast under the statistical model; its width conveys precision. No such estimate or interval is reported, so neither the magnitude nor precision of a treatment contrast can be judged.
The safety records list serious adverse events and other adverse events by treatment group, alongside deaths. Those counts are descriptive safety information, not evidence about the primary BNSS endpoint. Serious adverse events were recorded in some groups and not others; the listed deaths occurred in the Part B add-on placebo group. These observations alone do not establish that treatment caused or prevented an event. The registry record does not report event-level narratives, exposure-adjusted rates, statistical comparisons, or causal assessments.
The study's status is terminated, but that status alone does not explain why the study ended or imply a particular result. The registry record does not report a reason for termination, interim analysis findings, or a decision rule. It also does not report whether the study was stopped early relative to a planned schedule. Such details should not be inferred from status alone.
The available information therefore permits a description of the question, scale, groups, and some safety counts, but not a conclusion about treatment effect. Absence of a reported analysis is not evidence of no effect, and it is not evidence of benefit. It means the direction, size, and uncertainty of the primary comparison are not reported in the registry record.
9. Statistical Methods Explained
The statistical information is limited: the registry record identifies a continuous primary measure summarized as a mean with standard deviation, but reports 0 analyses. The endpoint is framed from baseline to Week 12. The following concepts explain how such results are commonly read in general; they do not describe an analysis confirmed to have been used in this study.
What does a mean and standard deviation describe?
For a continuous outcome, a mean is the arithmetic average of the observed scores in a group. The standard deviation describes how dispersed individual scores are around that mean. A mean alone does not reveal whether observations are tightly clustered or widely spread; the standard deviation adds information about variability. Neither quantity alone gives a treatment comparison. To compare randomized groups, an analysis usually estimates a contrast, such as a difference in mean change or a difference in mean score at a specified time.
The BNSS total and avolition/apathy scores have bounded ranges stated in the registry record. A mean can be useful for summarizing a group, but it does not show the score distribution, the number of participants contributing at each time point, or whether the average masks different patterns among participants. Those distributional details are not reported in the registry record.
What would a treatment contrast mean?
A treatment contrast compares an outcome under one assigned group with an outcome under a comparator group. In a randomized study, such a contrast can support an estimate of the difference associated with assignment, subject to the analysis population, missing observations, adherence, and other design details. The exact contrast matters. A Week 12 endpoint comparison is not identical to a comparison of change from baseline, and a contrast in Part A monotherapy is not automatically equivalent to one in Part B add-on therapy.
The registry record gives a baseline-to-Week 12 timeframe but does not specify whether the intended contrast was based on change scores, Week 12 scores adjusted for baseline, a repeated-measures model, or another approach. It also does not report whether Parts A and B were analyzed separately or together. No treatment contrasts are posted, so none can be reconstructed.
How should uncertainty be read?
A confidence interval is an interval estimate that represents uncertainty around an estimated quantity under the assumptions of the statistical method. A narrow interval indicates greater precision than a wide interval, while an interval spanning values in different directions may leave the direction of an effect uncertain. The interval's interpretation depends on the model and study design. General statistical interpretation should consider both the estimated effect and its uncertainty rather than treating a single significance threshold as a complete account of the evidence.
No confidence interval or p-value for the primary outcome is reported in the registry record. It is therefore not possible to evaluate statistical compatibility with a null contrast, estimate precision, or distinguish a small effect from a large but imprecise estimate. No numerical inference should be derived from the enrollment count alone.
Why does the analysis population matter?
The primary outcome description defines a modified intent-to-treat population as all randomized participants who received at least one dose of study drug. This definition indicates that randomization alone was not sufficient for inclusion in that population. It does not state how participants with missing measurements, protocol deviations, or treatment discontinuation were handled. The registry record does not report the number analyzed for each outcome or by group.
Analysis populations can affect interpretation because excluding participants after randomization may alter the balance created by random assignment. A modified intent-to-treat definition is not interchangeable with an all-randomized analysis or a per-protocol analysis. The record does not identify additional analysis populations or explain whether sensitivity analyses were undertaken.
What can be inferred from the sample-size assumptions?
The record describes planning illustrations based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. These are stated assumptions for illustrations, not the trial's own documented design justification. The registry record does not report the original sample-size calculation, its target effect, or a statistical power target used to plan the trial.
Sample-size illustrations are conditional on their assumptions. Changing the effect targeted, variability, allocation, or analysis method can change the number of participants needed. They are not observed power and do not establish whether an observed result is credible or important. Since no primary outcome effect estimate is reported, the planning illustrations cannot be interpreted as evidence about the treatment effect in this registry record.
Why might outcome distributions require attention?
General methods for continuous outcomes often rely on assumptions about the distribution of residuals and the adequacy of the chosen model. If observations are more variable than a model anticipates, standard errors can be understated and confidence intervals too narrow; this is one form of over-dispersion. The appropriate response depends on the data and design, and may involve a different model or variance estimate. The registry record does not provide participant-level data, distributional summaries, diagnostic checks, or a model specification, so it is not possible to assess whether these issues arose.
Likewise, repeated measurements on the same participant are correlated rather than independent. A method analyzing baseline and follow-up together should account for that structure. This is a general consideration for repeated outcome measurements, not a claim about the method used in this study. The statistical model and handling of within-participant correlation are not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists several secondary outcomes, including Clinical Global Impression severity and improvement scores, PANSS total and symptom factor scores, BNSS total score, and DPAS scores. It reports 13 outcome measures and 0 analyses. The primary outcome itself refers to both an avolition/apathy subscore and a total score, with measurements at baseline and Week 12. This creates multiple possible endpoints, time points, and treatment comparisons to consider.
In general, when many outcomes or comparisons are examined, the chance of at least one apparently unusual result can increase. Statistical approaches can address multiplicity through prespecified testing sequences, adjusted significance thresholds, or other methods. Which approach is appropriate depends on the study's aims and analysis plan. The registry record does not report a multiplicity strategy, hierarchy of endpoints, or prespecified primary contrast. It also does not report whether any secondary outcome results were analyzed or selected for reporting.
Missing outcome data can affect both the estimated treatment contrast and its uncertainty. Common methods make assumptions about why values are missing and use those assumptions in the analysis. A complete-case analysis, a likelihood-based repeated-measures method, and an imputation approach can answer related but not identical questions. These are general examples, not methods attributed to this trial. The registry record does not report missing-data counts, reasons for missingness, imputation procedures, sensitivity analyses, or follow-up completeness.
The stated modified intent-to-treat population includes randomized participants who received at least one dose. The record does not report how that population was applied to each endpoint or whether any additional exclusions occurred. It therefore does not permit assessment of the impact of missing data, post-randomization exclusions, or analytic choices on the reported results. With no posted analyses, multiplicity and missing-data handling remain unreported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Part A: Monotherapy (Placebo) | 0 | 15 | 0.0% |
| Part A: Monotherapy (150 mg) | 1 | 12 | 8.3% |
| Part B: Add-on Therapy (Placebo) | 1 | 37 | 2.7% |
| Part B: Add-on Therapy (45 mg) | 0 | 5 | 0.0% |
| Part B: Add-on Therapy (150 mg) | 2 | 30 | 6.7% |
| Part B: Add-on Therapy (300 mg) | 0 | 32 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Part A: Monotherapy (Placebo) | 0 of 15 |
| Part A: Monotherapy (150 mg) | 0 of 12 |
| Part B: Add-on Therapy (Placebo) | 1 of 37 |
| Part B: Add-on Therapy (45 mg) | 0 of 5 |
| Part B: Add-on Therapy (150 mg) | 0 of 30 |
| Part B: Add-on Therapy (300 mg) | 0 of 32 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Part A: Monotherapy (Placebo) | 7 of 15 |
| Part A: Monotherapy (150 mg) | 4 of 12 |
| Part B: Add-on Therapy (Placebo) | 9 of 37 |
| Part B: Add-on Therapy (45 mg) | 2 of 5 |
| Part B: Add-on Therapy (150 mg) | 8 of 30 |
| Part B: Add-on Therapy (300 mg) | 4 of 32 |
Most frequent serious adverse event terms
| Event term | Organ system | Part A: Monotherapy (Placebo) | Part A: Monotherapy (150 mg) | Part B: Add-on Therapy (Placebo) | Part B: Add-on Therapy (45 mg) | Part B: Add-on Therapy (150 mg) | Part B: Add-on Therapy (300 mg) |
|---|---|---|---|---|---|---|---|
| Accidental death | General disorders | 0 of 15 | 0 of 12 | 1 of 37 | 0 of 5 | 0 of 30 | 0 of 32 |
| Rhinovirus infection | Infections and infestations | 0 of 15 | 0 of 12 | 0 of 37 | 0 of 5 | 1 of 30 | 0 of 32 |
| Tumour haemorrhage | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 15 | 0 of 12 | 0 of 37 | 0 of 5 | 1 of 30 | 0 of 32 |
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 0 of 15 | 0 of 12 | 0 of 37 | 0 of 5 | 1 of 30 | 0 of 32 |
| Constipation | Gastrointestinal disorders | 0 of 15 | 1 of 12 | 0 of 37 | 0 of 5 | 0 of 30 | 0 of 32 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Part A: Monotherapy (Placebo) | Part A: Monotherapy (150 mg) | Part B: Add-on Therapy (Placebo) | Part B: Add-on Therapy (45 mg) | Part B: Add-on Therapy (150 mg) | Part B: Add-on Therapy (300 mg) |
|---|---|---|---|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 0 of 15 | 0 of 12 | 2 of 37 | 0 of 5 | 3 of 30 | 3 of 32 |
| Dizziness | Nervous system disorders | 0 of 15 | 0 of 12 | 1 of 37 | 0 of 5 | 2 of 30 | 1 of 32 |
| Headache | Nervous system disorders | 0 of 15 | 0 of 12 | 3 of 37 | 0 of 5 | 1 of 30 | 0 of 32 |
| Nausea | Gastrointestinal disorders | 0 of 15 | 2 of 12 | 0 of 37 | 0 of 5 | 1 of 30 | 1 of 32 |
| Fatigue | General disorders | 0 of 15 | 0 of 12 | 1 of 37 | 0 of 5 | 2 of 30 | 0 of 32 |
| Upper respiratory tract infection | Infections and infestations | 2 of 15 | 0 of 12 | 0 of 37 | 1 of 5 | 0 of 30 | 0 of 32 |
| Somnolence | Nervous system disorders | 0 of 15 | 0 of 12 | 2 of 37 | 0 of 5 | 1 of 30 | 0 of 32 |
| Rash | Skin and subcutaneous tissue disorders | 0 of 15 | 0 of 12 | 0 of 37 | 0 of 5 | 1 of 30 | 2 of 32 |
| Insomnia | Psychiatric disorders | 1 of 15 | 2 of 12 | 0 of 37 | 0 of 5 | 0 of 30 | 0 of 32 |
| Decreased appetite | Metabolism and nutrition disorders | 1 of 15 | 0 of 12 | 1 of 37 | 0 of 5 | 1 of 30 | 0 of 32 |
Serious events with the highest arm-level rate: constipation (8.3%), rhinovirus infection (3.3%), tumour haemorrhage (3.3%), chronic obstructive pulmonary disease (3.3%), accidental death (2.7%).
The registry record reports serious adverse event counts by treatment group, with the number at risk also listed. Part A monotherapy placebo had 0 serious events among 15 at risk, and Part A monotherapy 150 mg had 1 among 12. For Part B add-on therapy, placebo had 1 among 37, 45 mg had 0 among 5, 150 mg had 2 among 30, and 300 mg had 0 among 32. The record lists 1 death in the Part B add-on placebo group and 0 in each other group.
These are descriptive counts. They do not by themselves show whether an event was caused by treatment, whether groups differed statistically, or whether differences are meaningful. The groups have different numbers at risk, and the record does not provide exposure time or an adjusted comparison. Counts of zero do not establish that an event cannot occur.
The registry also lists serious-event terms with percentages: Constipation, 8.3%; Rhinovirus infection, 3.3%; Tumour haemorrhage, 3.3%; Chronic obstructive pulmonary disease, 3.3%; and Accidental death, 2.7%. The denominators and the relationship between these percentages and individual treatment groups are not reported in the registry record. These terms should not be interpreted as comparative risks without those details.
Other adverse events are separately counted for each group, but the record does not identify event types for those counts in the information. Serious and other adverse event categories are distinct summaries and should not be combined. The safety counts do not answer the primary BNSS efficacy question.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study was designed to compare RO6889450 with placebo in a randomized, quadruple-masked, parallel-group Phase 2 study. It identifies monotherapy and add-on therapy settings and names BNSS scores from baseline to Week 12 as the primary outcome. It also describes how the BNSS total and avolition/apathy subscore are constructed. These design and measurement details clarify what the study set out to examine.
They do not establish what the outcome was. No primary outcome values, treatment contrasts, confidence intervals, or p-values are reported, and the record lists 0 analyses. Therefore, the direction and magnitude of a difference between RO6889450 and placebo are not reported in the registry record. The absence of posted results should not be recast as a finding of no difference, just as the study's randomized design should not be treated as evidence of a benefit.
The safety section records serious adverse event counts, other adverse event counts, deaths, and a list of serious-event terms with percentages. Those observations can describe what the registry lists, but they do not establish causality or provide a complete comparison of safety. The record does not report exposure-adjusted analyses, event narratives, or statistical comparisons. Group sizes and treatment contexts differ, and the listed percentages have no stated denominators in the record.
The study status is terminated. That label does not reveal the reason for termination or what the investigators concluded. The registry record does not report those details, nor does it report an interim analysis or its findings. Any explanation for termination would be speculation.
In short, the record supports a description of the planned clinical question and available registry-level safety counts. It does not support a claim that RO6889450 changed negative symptoms, nor a claim that it had no effect. A treatment conclusion would require interpretable outcome estimates and their uncertainty, together with information on analysis populations, missing data, and the analysis plan.
13. Why This Trial Matters Statistically
This trial is statistically notable for the gap between a clearly described clinical endpoint and the absence of posted outcome analyses. The registry identifies a specific symptom scale, two BNSS components, and a baseline-to-Week 12 timeframe. It also defines a modified intent-to-treat population. Those details give a reader a framework for understanding what an eventual estimate would represent, but without the estimate they cannot answer the comparative question.
The study has multiple treatment contexts. Part A evaluates monotherapy, whereas Part B evaluates add-on therapy alongside usual antipsychotic treatment(s). Interpreting these settings requires attention to which groups are compared and whether an analysis combines or separates them. The registry record does not report such an analysis. This limits the ability to distinguish a dose-specific finding from a broader claim about the intervention.
The endpoint includes both a focused subscore and a total score, and the registry lists multiple secondary outcomes. In general, multiple endpoints raise questions about which comparison is primary and how uncertainty from multiple testing is handled. The record does not report the statistical plan or multiplicity approach. This is important because isolated results across many outcomes should not be read as if only one comparison had been made.
Finally, the listed safety counts and terminated status add context but do not fill the efficacy reporting gap. Statistical interpretation depends not only on the design but also on estimates, precision, missing-data handling, and transparent analysis methods. Those elements are not reported in the registry record. The case therefore illustrates why trial registration details and outcome analyses serve different purposes: one can describe the intended study question without providing evidence that answers it.
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 principal limitation for interpretation is that the registry record reports no outcome analyses. It provides no BNSS values at baseline or Week 12, no changes by group, and no estimated treatment contrasts. Without those results, effect magnitude, direction, and precision cannot be evaluated. The record also does not report confidence intervals, p-values, or the number of participants contributing to each endpoint analysis.
The primary outcome covers both the avolition/apathy subscore and total score across time points. The record notes that the outcome has several categories or time points and does not reduce it to a single comparison. It does not identify which specific contrast should be treated as the principal inferential result. No statistical analysis plan, model specification, covariate strategy, or multiplicity method is reported.
The modified intent-to-treat population is defined, but missing-data handling and analytic exclusions are not reported. The record does not state how participants without Week 12 scores were treated, whether additional populations were analyzed, or whether sensitivity analyses were conducted. These omissions prevent assessment of the robustness of any efficacy analysis, were one to be posted elsewhere.
The safety information is limited to group counts and listed event terms. Exposure time, event-level descriptions, denominators for the listed percentages, and comparative safety analyses are not reported in the registry record. The reason for termination is also not reported in the registry record. These are limitations of what can be concluded from this registry information, not evidence that any particular analysis or result is absent from all other sources.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Assess the Effects of RO6889450 (Ralmitaront) in Participants With Schizophrenia or Schizoaffective Disorder and Negative Symptoms — NCT03669640.
- Registry record last updated 2024-08-12; status last verified 2024-08.
- Results first posted 2024-08-12.
- 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.
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18. Record Summary
NCT03669640 is a Phase 2 randomized, quadruple-masked, parallel-group, placebo-controlled study sponsored by Hoffmann-La Roche. It concerns RO6889450 in participants with schizophrenia or schizoaffective disorder and negative symptoms. The registry lists enrollment of 131, a start date of 2018-12-04, primary completion on 2023-03-12, and status as terminated.
Part A studied monotherapy; Part B studied add-on therapy to usual antipsychotic treatment(s). The primary outcome was BNSS avolition/apathy subscore and total score from baseline to Week 12. The registry defines the BNSS and describes the modified intent-to-treat population, but reports 0 analyses. Consequently, no primary outcome treatment effect or precision estimate is available in the registry record. Safety counts and serious-event terms are listed, but they do not replace an efficacy analysis or establish causality.