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 Phase 3 Study To Evaluate The Efficacy And Safety Of TNX-102 SL In Patients With Fibromyalgia (NCT04508621), a randomized phase 3 study. The primary outcome is Change From Baseline to Week 14 in the Numerical Rating Scale (NRS) Weekly Average of Daily Self-reported Average Pain Severity Scores..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04508621 |
| Phase | Phase 3 |
| Condition | Fibromyalgia |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 514 |
| Arms in the primary outcome | 2 |
| Lead sponsor | Tonix Pharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with fibromyalgia were eligible for the trial. The primary analysis population was the intent-to-treat population, defined in the registry record as all randomized patients. The record reports enrollment of 514 participants and states that missing primary outcome data were addressed with multiple imputation.
Intervention
Participants assigned to TNX-102 SL took sublingual tablets at bedtime. The treatment schedule began with one 2.8 mg tablet daily for 2 weeks, followed by two 2.8 mg tablets, for a total dose of 5.6 mg, daily for 12 weeks.
Comparator
The comparison group received placebo tablets sublingually at bedtime on the same schedule: one tablet daily for 2 weeks, followed by two tablets daily for 12 weeks. The study was placebo-controlled and quadruple-masked, according to the registry record.
Primary question
The primary question was whether change from baseline to Week 14 in the weekly average of daily self-reported pain severity differed between TNX-102 SL and placebo. Pain was recorded in an electronic diary on an 11-point numerical rating scale, from 0 for no pain to 10 for worst possible pain. The registry reports least-squares mean changes and a mixed model repeated measures comparison between groups.
3. Trial Design
This was a Phase 3, randomized, parallel-group, double-blind, multicenter, placebo-controlled study of TNX-102 SL in patients with fibromyalgia. The registry record lists the trial as completed, with enrollment of 514 participants. The stated study duration was 14 weeks. The listed start date is 2020-07-22, and the primary completion date is 2021-11-01.
Participants were assigned to TNX-102 SL or placebo. Both treatments were taken sublingually each day at bedtime. In each group, the schedule began with one tablet daily for 2 weeks and then increased to two tablets daily for 12 weeks. The TNX-102 SL group received 2.8 mg tablets, reaching a daily dose of 5.6 mg in the latter part of the schedule; the placebo group followed the matching tablet schedule.
The primary outcome was change from baseline to Week 14 in the weekly average of daily pain severity scores. The registry identifies the primary analysis population as all randomized patients and states that multiple imputation was used for missing data. The analysis method reported for the comparison was mixed model repeated measures. Further details of randomization procedures, the masking roles, site count, allocation ratio, protocol deviations, and the model’s covariates are not reported in the registry record.
The registry lists six secondary outcomes addressing global impression of change, fibromyalgia symptoms and function, sleep disturbance, fatigue, and sleep quality. The posted results include a comparison for the global impression outcome. Numerical results for the remaining secondary outcomes 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.
Overall Study
| Stage | TNX-102 SL Tablet, 5.6 mg | Placebo SL Tablet |
|---|---|---|
| STARTED | 256 | 258 |
| COMPLETED | 189 | 210 |
| NOT COMPLETED | 67 | 48 |
Reasons for not completing this period:
| Reason | TNX-102 SL Tablet, 5.6 mg | Placebo SL Tablet |
|---|---|---|
| Adverse Event | 39 | 16 |
| Lack of Efficacy | 2 | 8 |
| Physician Decision | 0 | 1 |
| Withdrawal by Subject | 10 | 14 |
| Lost to Follow-up | 12 | 9 |
| COVID-19 related crisis | 3 | 0 |
| Subject non-compliance | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Intent to treat population (all patients who were randomized). Multiple imputation for missing data.
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.
| Characteristic | Unit | TNX-102 SL Tablet, 5.6 mg | Placebo SL Tablet | Total |
|---|---|---|---|---|
| Participants analysed | 256 | 258 | 514 | |
| Age, Continuous | years | 48.9 (SD 10.55) | 48.5 (SD 10.60) | 48.7 (SD 10.57) |
| Sex: Female, Male: Female | Participants | 242 | 245 | 487 |
| Sex: Female, Male: Male | Participants | 14 | 13 | 27 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Asian | Participants | 5 | 1 | 6 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 3 | 3 |
| Race (NIH/OMB): Black or African American | Participants | 16 | 24 | 40 |
| Race (NIH/OMB): White | Participants | 226 | 223 | 449 |
| Race (NIH/OMB): More than one race | Participants | 6 | 6 | 12 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 1 | 1 | 2 |
| Region of Enrollment: United States | participants | 256 | 258 | 514 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline to Week 14 in the Numerical Rating Scale (NRS) Weekly Average of Daily Self-reported Average Pain Severity Scores., measured over 14 weeks.
| Element | Registry entry |
|---|---|
| Result type | Least Squares Mean |
| Measure of spread | 95% Confidence Interval |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint measures change from baseline to Week 14 in the weekly average of daily self-reported average pain severity. Participants recorded their average pain over the prior 24 hours in an electronic diary. The rating scale runs from 0, meaning no pain, to 10, meaning worst possible pain. The outcome therefore captures a participant-reported symptom over repeated diary assessments rather than a single measurement at the end of the study.
Repeated daily recording can describe pain across the assessment period and may reduce reliance on one isolated recollection. Averaging the diary assessments into a weekly value also gives the analysis a defined summary of reported pain. These are general reasons for using repeated patient-reported measures; the registry does not state the investigators’ rationale for selecting this particular endpoint.
The endpoint is expressed as change from baseline, so negative values indicate lower pain scores at Week 14 relative to baseline. The registry reports least-squares means and 95% confidence intervals for each group, then a model-based difference between groups. Those group changes describe how scores shifted within each arm; the between-group comparison is the relevant estimate for the randomized treatment contrast. A change within one arm alone does not establish that the change differs from what occurred in the comparison arm.
The registry does not report a threshold for a clinically important difference on this scale. The magnitude of a numerical change should therefore be read as a score change, not as a determination of clinical importance.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The reported primary group estimates were a least-squares mean change of -1.6 for TNX-102 SL, with a 95% confidence interval from -1.8 to -1.3, and -1.3 for placebo, with a 95% confidence interval from -1.5 to -1.1. Both estimates describe reductions from baseline in the pain score. The within-group changes are not themselves the randomized comparison: the main question is whether the change differed between groups.
The registry’s mixed model repeated measures result gives a least-squares mean difference of -0.2, with a 95% confidence interval from -0.6 to 0.1 and p = 0.115. The estimate favors a greater reduction in the TNX-102 SL group on the score’s direction, but the interval includes zero. Thus, the posted estimate is compatible with a range of between-group effects that includes no difference. The p-value does not provide strong evidence against a no-difference null hypothesis under the reported analysis.
A confidence interval represents the uncertainty around an estimated effect under the analysis model. It is not a range containing a known fixed effect with certainty, and it does not measure the probability that the treatment effect lies at a particular value. The interval’s inclusion of zero means that the registry’s estimate is not precise enough to exclude no between-group difference at the conventional 5% significance threshold. That threshold is a general reference; the primary significance threshold specified in the protocol is not reported in the registry record.
The registered outcome is patient-reported pain, and the point estimate is on the original score scale. The registry does not state a threshold for a clinically meaningful difference, so statistical evidence and clinical importance cannot be equated from these data alone. Nor do the posted results establish that any observed within-arm improvement was caused by the assigned treatment: changes may also reflect effects common to both groups, such as participation and assessment over time.
Interpretation is also bounded by the registry’s reporting detail. It identifies the intent-to-treat population and multiple imputation, but does not report the imputation model, assumptions, covariates, or sensitivity analyses. The overall conclusion should therefore stay close to the reported comparison: the estimated between-group difference was -0.2, its 95% confidence interval included zero, and the reported p-value was 0.115.
9. Statistical Methods Explained
The primary result combines a repeated-measures model with a summary estimate of the treatment contrast. Understanding what that estimate represents helps distinguish the trial’s main comparison from changes within each treatment group.
What does a least-squares mean represent?
A least-squares mean is a model-based estimate of an outcome mean. In general, it can account for terms included in the statistical model and is not necessarily the same as a simple arithmetic average of all observed values. The registry reports least-squares mean changes for each group and a least-squares mean difference between groups. It does not identify the model’s covariates or give enough detail to reconstruct the adjusted estimates from participant-level data.
The reported group estimates are -1.6 for TNX-102 SL and -1.3 for placebo. The treatment contrast is reported separately as -0.2. These are not interchangeable quantities: the first two describe model-based average changes in their respective groups, while the contrast estimates the difference between groups under the fitted analysis.
Why use mixed model repeated measures?
Mixed model repeated measures is a general approach for analysing outcome measurements collected over time. It can use repeated observations and account for their statistical relationship within a participant. It can also estimate differences at specified assessment times, depending on the model specification. The registry names this method for the primary comparison, but does not report its covariance structure, fixed effects, covariates, or other implementation details. Those features should not be inferred from the method’s name alone.
The primary endpoint is a change from baseline in weekly averages of daily diary scores, assessed through Week 14. Repeated observations can provide information about the pattern across follow-up rather than relying solely on one end-point measurement. In general, a repeated-measures model’s validity depends on its specification and on assumptions about the data, including how missing observations relate to observed information. The registry does not provide enough detail to assess those assumptions fully.
How should the confidence interval and p-value be read?
The primary 95% confidence interval for the between-group difference is -0.6 to 0.1. In general, a confidence interval expresses the precision of an estimate under the analysis assumptions: a narrower interval indicates greater precision than a wider interval, all else equal. It does not establish clinical importance. Because this interval includes zero, the data do not rule out a null difference under the reported model at the corresponding conventional confidence level.
The reported p-value is 0.115. A p-value describes how incompatible the observed data are with a specified null hypothesis under the model assumptions; it is not the probability that the null hypothesis is true, nor the probability that the result occurred by chance. The registry does not report a full statistical analysis plan, so the precise prespecified decision rules cannot be confirmed from the record.
What does multiple imputation contribute?
The registry says multiple imputation was used for missing primary outcome data in the intent-to-treat population, which includes all randomized patients. In general, multiple imputation fills in missing values through a statistical procedure that represents uncertainty about those values, rather than treating a single filled-in value as known. Its reliability depends on the imputation model and assumptions about why values are missing. The registry does not report the imputation variables, number of imputations, missingness assumptions, or sensitivity analyses. The method’s mention alone is not enough to establish how robust the result is to missing-data assumptions.
How do the secondary comparison and planning illustrations differ?
The registry reports a Pearson chi-squared analysis for the secondary outcome counting participants rated much improved or very much improved. This is a categorical outcome, so the reported comparison is a difference in proportions. The sponsor-reported estimate is 8.0, with a 95% confidence interval from 0.5 to 15.5 and p = 0.038. A separate unadjusted recalculation is a direct comparison based on the posted counts; it does not replace the sponsor’s analysis or adjust for other factors.
The sample-size illustrations are planning exercises based on the observed effect, not observed power and not the trial’s own sample-size justification. They describe participants per arm under stated assumptions: two-sided significance level 0.05, equal allocation, and a normal approximation. The illustrations consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. For 80% power, the listed participants per arm are 470, 814, and 1,781, respectively; for 90% power, they are 628, 1,089, and 2,384, respectively. Smaller assumed effects require larger planning samples under these assumptions. The registry’s own design rationale and sample-size justification are not reported in the registry record.
10. Analyses Reported by the Sponsor
| Method | Estimate | 95% CI | P-value |
|---|---|---|---|
| Mixed Model Repeated Measures | LS Mean Difference -0.2 | -0.6 to 0.1 | 0.115 |
The sponsor’s primary analysis is the mixed model repeated measures comparison reported in the registry record. It estimates a least-squares mean difference of -0.2, with a 95% confidence interval from -0.6 to 0.1 and p = 0.115. That analysis is the principal posted result for the primary endpoint. The registry record does not flag a discrepancy between the sponsor result and any recalculation.
For the secondary global impression outcome, the sponsor reports a Pearson chi-squared analysis with a difference in proportions of 8.0, a 95% confidence interval from 0.5 to 15.5, and p = 0.038. The unadjusted recalculation uses the posted counts and reports a risk difference on a proportion scale. Because the two presentations use different scales and the recalculation is unadjusted, they should not be treated as identical methods or as a replacement for the sponsor’s analysis. The registry record does not flag a discrepancy for this comparison.
The sponsor’s own analysis takes precedence when a discrepancy is flagged; no such flag is recorded. Even without a flagged discrepancy, the model-based primary result and the unadjusted secondary recalculation answer their respective questions using different methods. The recalculation is a check based on summary counts, not a reproduction of the sponsor’s full analysis, and it cannot account for model details that are not reported.
11. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when a study evaluates several outcomes, time points, groups, or analyses and then interprets their results together. Even when each individual test uses a conventional significance threshold, looking across many tests can make at least one small p-value more likely under a setting where none of the tested effects is real. This general statistical concern is relevant because the registry lists a primary outcome and six secondary outcomes.
The registry does not report whether the statistical plan used a hierarchy of tests, an adjustment for multiple comparisons, or another procedure to control the overall error rate. The reported p-value for the secondary global impression outcome is therefore an unadjusted result unless the registry specifies otherwise; no adjustment is described. It should not be interpreted with the same confirmatory weight as a prespecified primary analysis without knowing the planned testing strategy. The record also does not report numerical results for the other secondary outcomes, limiting assessment of the broader pattern.
Missing data are another important issue. The primary analysis population is described as all randomized patients, and multiple imputation was used for missing primary outcome data. In general, this approach can preserve uncertainty from imputed values, but its validity depends on the model and assumptions. The registry does not report the amount or timing of missing outcome data, the imputation model, the variables included, or analyses testing alternative assumptions. It is therefore not possible to judge from the registry record how sensitive the primary estimate is to missingness.
The registry identifies the intent-to-treat population for the primary outcome. Details of any additional analysis populations, exclusions after randomization, or per-protocol analyses are not reported in the registry record. Interim analyses and any stopping rules are also not reported. These omissions do not show that such procedures were or were not used; they mean the posted record does not describe them. Without the full protocol or statistical analysis plan, the multiplicity strategy, missing-data assumptions, and analysis-population decisions cannot be fully evaluated.
12. 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 |
|---|---|---|---|
| TNX-102 SL Tablet, 5.6 mg | 6 | 256 | 2.3% |
| Placebo SL Tablet | 0 | 258 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| TNX-102 SL Tablet, 5.6 mg | 0 of 256 |
| Placebo SL Tablet | 0 of 258 |
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 |
|---|---|
| TNX-102 SL Tablet, 5.6 mg | 80 of 256 |
| Placebo SL Tablet | 5 of 258 |
Most frequent serious adverse event terms
| Event term | Organ system | TNX-102 SL Tablet, 5.6 mg | Placebo SL Tablet |
|---|---|---|---|
| COVID-19 pneumonia | Infections and infestations | 1 of 256 | 0 of 258 |
| Localized infection | Infections and infestations | 1 of 256 | 0 of 258 |
| Pneumonia | Infections and infestations | 1 of 256 | 0 of 258 |
| Pancreatitis | Gastrointestinal disorders | 1 of 256 | 0 of 258 |
| Bile duct stone | Hepatobiliary disorders | 1 of 256 | 0 of 258 |
| Forearm fracture | Injury, poisoning and procedural complications | 1 of 256 | 0 of 258 |
| Invasive ductal breast carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 256 | 0 of 258 |
Most frequent non-serious adverse event terms
| Event term | Organ system | TNX-102 SL Tablet, 5.6 mg | Placebo SL Tablet |
|---|---|---|---|
| Hypoaesthesia oral | Gastrointestinal disorders | 72 of 256 | 2 of 258 |
| Product taste abnormal | Product Issues | 26 of 256 | 2 of 258 |
| Oral discomfort | Gastrointestinal disorders | 23 of 256 | 2 of 258 |
| Tongue discomfort | Gastrointestinal disorders | 16 of 256 | 2 of 258 |
Serious events with the highest arm-level rate: covid-19 pneumonia (0.4%), localized infection (0.4%), pneumonia (0.4%), pancreatitis (0.4%), bile duct stone (0.4%).
The registry reports serious adverse events for 6 participants in the TNX-102 SL group and 0 participants in the placebo group. It reports other adverse events for 80 participants assigned to TNX-102 SL and 5 assigned to placebo. No deaths are reported in either group. The registry lists several serious adverse event terms at 0.4% each, including COVID-19 pneumonia, localized infection, pneumonia, pancreatitis, bile duct stone, and forearm fracture.
These figures describe events recorded during the study; they do not by themselves establish that treatment caused an event. The registry does not provide event-level timing, duration, outcome, relatedness assessments, or enough detail to determine whether participants experienced more than one event. The counts should therefore be read as reported participant figures rather than as a complete characterization of each event or its causal relationship to treatment.
The comparison also comes from a trial with 514 enrolled participants and a 14-week study duration. Such registry counts are descriptive and do not, on their own, determine the frequency of uncommon harms or the safety profile beyond the observed study period. Further safety details are not reported in the registry record.
13. What the Result Does, and Does Not, Mean
The primary result estimates the between-group difference in change in diary-based pain scores at Week 14. The reported least-squares mean difference is -0.2, with a 95% confidence interval from -0.6 to 0.1 and p = 0.115. The estimate points toward a larger average reduction in the TNX-102 SL group, but the interval includes zero and the p-value does not provide strong evidence of a difference under the reported analysis.
This does not mean the two groups are proven identical. A confidence interval that includes zero indicates uncertainty: the data remain compatible with no difference and with effects in either direction within the interval. Nor does the result prove that there is no treatment effect. It describes the estimate and its precision given this study and the reported model.
The group-level changes were negative in both arms. A within-group reduction is not the same as a treatment effect because the randomized contrast asks whether the change differs between TNX-102 SL and placebo. The registry’s primary comparison is the appropriate result for that question. The record does not report a clinically important difference threshold, so the score estimate cannot be classified as clinically meaningful based on a threshold in the registry.
The secondary global impression outcome has a reported p-value of 0.038, but it is one finding among multiple listed secondary outcomes, and the multiplicity plan is not reported. Numerical results for the other secondary outcomes are also not reported in the registry record. That finding is therefore not enough to establish a consistent benefit across outcomes or to override the primary comparison.
Finally, the results apply to the population, follow-up period, outcome definitions, and analysis described in the registry record. They do not establish effects beyond the 14-week study, and the registry does not give enough methodological detail to fully evaluate missing-data assumptions or the broader analysis plan. The findings should be read as estimates with uncertainty, not as a complete account of efficacy, clinical importance, or safety.
14. Why This Trial Matters Statistically
This trial illustrates why a clinical result should be read through its between-group estimate and its uncertainty, rather than by looking only at whether each group changed from baseline. Both groups had negative mean changes in the primary pain score, but the randomized question is the difference between those changes. The reported contrast is -0.2, and its 95% confidence interval extends from -0.6 to 0.1. That interval makes precision central to the interpretation: the point estimate alone does not tell the whole story.
The trial also shows how results from different outcome types can answer related but nonidentical questions. Daily pain ratings summarize symptom severity over repeated assessments, while the global impression measure records a participant’s overall judgment of improvement. A positive-looking secondary comparison does not automatically resolve uncertainty in the primary endpoint. Multiplicity and the availability of results across the other secondary domains matter when judging whether findings form a coherent pattern.
Missing-data methods are part of the interpretation as well. The registry identifies multiple imputation for the primary outcome, but does not report enough detail to assess its assumptions or robustness. This is a reminder that naming an analysis method is not the same as documenting all the choices needed to evaluate it.
Finally, the record distinguishes a trial result from a planning exercise. Sample-size illustrations based on observed effects can show how assumptions about an effect size relate to a planned sample, but they are not observed power and do not explain the trial’s original design decisions. The trial-specific sample-size justification is not reported in the registry record.
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.
Several trial-specific limitations in the registry record constrain interpretation. First, the primary confidence interval includes zero, and the reported p-value is 0.115. The estimate therefore has uncertainty that does not exclude no between-group difference. The registry does not provide a clinically important difference threshold, which prevents a registry-based judgment about whether the point estimate would matter to patients.
Second, key implementation details are not reported. The registry names mixed model repeated measures and multiple imputation but does not describe model covariates, covariance structure, imputation variables, missingness assumptions, or sensitivity analyses. The amount and timing of missing data are also not reported. These gaps limit independent assessment of how much the primary result depends on analytical choices.
Third, the record does not report the statistical plan for multiplicity, the primary significance threshold, or a hierarchy for the secondary outcomes. The global impression result is one secondary finding, while numerical results for the other listed secondary outcomes are not reported. This prevents a complete assessment of whether evidence across the prespecified outcome domains is consistent.
The registry does not report detailed participant characteristics, site information, adherence, treatment discontinuations, protocol deviations, or the reasons for missing data. It also does not report interim analyses or stopping rules. These items should not be assumed to have been absent; they are simply not described in the registry record.
Finally, safety information is limited to participant counts for serious and other adverse events and a short list of serious event terms. Timing, relatedness, event-level details, and outcomes are not reported. The study duration was 14 weeks, so the posted results do not describe outcomes beyond that follow-up period.
16. Related Tutorials
17. Related Statistical Calculators
18. Sources
- ClinicalTrials.gov: A Phase 3 Study To Evaluate The Efficacy And Safety Of TNX-102 SL In Patients With Fibromyalgia — NCT04508621.
- Registry record last updated 2023-12-18; status last verified 2023-12.
- Results first posted 2022-12-02.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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19. Record Summary
The registry record describes a completed Phase 3 randomized, parallel-group, quadruple-masked, placebo-controlled trial in patients with fibromyalgia. Enrollment was 514, and the treatment period was 14 weeks. Participants received bedtime sublingual TNX-102 SL or matching placebo, with a tablet schedule that increased after 2 weeks.
The primary endpoint was change from baseline to Week 14 in weekly average daily pain severity. The reported mixed model repeated measures difference was -0.2, with a 95% confidence interval from -0.6 to 0.1 and p = 0.115. The record also reports a secondary global impression comparison, but numerical results for the remaining listed secondary outcomes are not reported in the registry record.
The record identifies multiple imputation for missing primary data and lists serious and other adverse event counts. Further details of the statistical plan, multiplicity approach, missing-data assumptions, and sample-size justification are not reported in the registry record.