A Study of JNJ-61393215 in the Treatment of Depression: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of JNJ-61393215 in the Treatment of Depression (NCT04080752), a randomized phase 2 study. The primary outcome is Change From Baseline in Hamilton Depression Rating Scale-17 (HDRS-17) Total Score at Week 6.

2. Clinical Question

The question concerns the added study treatment while standard antidepressant treatment continued. It is not a comparison of JNJ-61393215 alone with no treatment: both groups were to receive their prescribed standard antidepressants. The registry describes the HDRS-17 as a clinician-administered measure of depression severity, with higher total scores representing greater severity. Thus, the outcome compares average change on that scale over the stated assessment period. It does not by itself describe every aspect of participants’ experience, other possible outcomes, or the safety profile.

3. Trial Design

The registry identifies this as a phase 2, randomized, double-blind, parallel-group study with placebo control. The study title describes a multicenter investigation of efficacy, safety, and tolerability. The registry lists an enrollment of 222 and a completed status. The listed study dates are 2019-09-17 for study start and 2021-09-02 for primary completion.

Participants assigned to the active-treatment arm were to receive JNJ-61393215 135 mg, described as 3 capsules of 45 mg, orally once daily for 6 weeks. They were also to continue their prescribed standard oral antidepressant without a dose change throughout the study. The placebo arm was to receive matching placebo for 6 weeks, with the same instruction to continue standard antidepressant treatment without a dose change. The registry calls the intervention an adjunctive treatment, consistent with this design.

Randomization is intended to create comparison groups whose measured and unmeasured characteristics are balanced on average, although it cannot guarantee that balance in a particular trial. Double masking is intended to limit the influence of treatment knowledge on participants’ experiences and assessments. The record does not report who was masked, how allocation was generated or concealed, or whether the masking was assessed. Details of the study’s original sample-size justification and its prespecified statistical plan are not reported in the registry record.

The primary endpoint was change from baseline to week 6 in HDRS-17 total score. The registry also lists anxiety, depression, and safety outcomes at other assessment times or in a subgroup. The primary analysis population was the enriched analysis set, defined by treatment exposure and baseline HDRS-17 criteria. The analysis population therefore does not simply encompass everyone counted in the registry’s overall enrollment. The record does not explain the relationship between that enrollment figure and the outcome-specific analysis counts.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The enriched analysis set (EAS) included all randomized participants who received at least 1 dose of study agent and had improvement in percent changes in HDRS17 total score less than (\<)25 percent (%) from screening to baseline and HDRS-17 total score greater than or equal to (\>=)18 at baseline. Here, 'N' (number of participants analyzed) signifies number of participants who were evaluable for this outcome measure.

5. Baseline Characteristics

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

Population: The safety analysis set included all randomized participants who received at least 1 dose of study agent.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Hamilton Depression Rating Scale-17 (HDRS-17) Total Score at Week 6, measured over Baseline and Week 6.

The primary endpoint is change from baseline to week 6 in total score on the 17-item Hamilton Depression Rating Scale, or HDRS-17. The scale is administered by a clinician and is designed to assess depression symptom severity. Its total score ranges from 0 to 52, with a higher score indicating greater depression severity. Each item is rated on a 3-point or 5-point scale; the total is formed from the item scores.

Change from baseline is used to describe how the measured score differs after treatment from the participant’s starting score. A negative change means the follow-up score is lower than baseline, which corresponds to a decrease on a scale where higher scores indicate greater severity. The endpoint compares the average change between randomized groups; it does not show whether every participant changed in the same direction or by the same amount.

A clinician-rated scale provides a structured way to assess symptoms using specified items and scoring rules. It is one measure of the treatment comparison, not a complete account of functioning, quality of life, or safety. The registry’s primary outcome is specifically the week 6 assessment. It should not be read as a claim about durability beyond that timeframe, since longer-term primary results are not reported in the registry record.

7. Results Posted in the Registry

• JNJ-61393215 135 Milligrams (mg): mean -9.40 versus -8.80 on control; difference -0.60 (95% CI -2.40 to 1.20), standardized effect d = -0.09; z-test p = 0.514.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • JNJ-61393215 135 Milligrams (mg): mean -10.30 versus -10.40 on control; difference 0.10 (95% CI -1.92 to 2.12), standardized effect d = 0.01; z-test p = 0.923.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between JNJ-61393215 135 Milligrams (mg) and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in HDRS-17 Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • JNJ-61393215 135 Milligrams (mg): mean -9.80 versus -8.80 on control; difference -1.00 (95% CI -2.87 to 0.87), standardized effect d = -0.15; z-test p = 0.295.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between JNJ-61393215 135 Milligrams (mg) and the control. The interval gives the range of effects that remain compatible with the data.

Change From Baseline in HAM-A Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • JNJ-61393215 135 Milligrams (mg): mean -10.90 versus -10.60 on control; difference -0.30 (95% CI -2.45 to 1.85), standardized effect d = -0.04; z-test p = 0.784.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between JNJ-61393215 135 Milligrams (mg) and the control. The interval gives the range of effects that remain compatible with the data.

The listed secondary outcomes cover anxiety symptoms, depression symptoms at additional assessment times, a subgroup with a baseline HAM-A score of at least 20, and treatment-emergent adverse events. The available continuous secondary summaries show estimated between-group differences that are small relative to the uncertainty intervals reported in the re-calculations; each interval spans zero. This broad pattern is consistent with the primary result in that the posted estimates do not establish a clear separation between arms. It does not demonstrate equivalence, and it does not establish that the groups had identical outcomes.

The secondary measures address related but distinct questions. HAM-A and GAD-7 assess anxiety symptoms, while HDRS-17 and PHQ-9 address depressive symptoms using their respective scales. A subgroup analysis restricted by baseline HAM-A score applies to a narrower population and should not be assumed to represent the full trial population. These outcomes can help describe the broader set of questions considered, but they do not replace the primary endpoint or resolve its uncertainty.

The registry lists additional secondary outcomes, but detailed numerical results for every listed outcome are not reported in the registry record. Sponsor analyses for the secondary outcomes are not reported in the registry record. Without complete outcome results and a stated multiplicity strategy, the overall pattern should be interpreted cautiously. When many outcomes or timepoints are examined, some apparent differences can arise by chance; unadjusted secondary results therefore carry less weight than a clearly specified primary comparison. The registry does not report whether or how the trial controlled for this multiplicity.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Change From Baseline in Hamilton Anxiety Rating Scale (HAM-A) Total Score at Week 6
• Change From Baseline in HAM-A Total Score at Weeks 2 and 4
• Change From Baseline in HDRS-17 Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6
• Change From Baseline in HAM-A Total Score in Participants With a Baseline HAM-A Score >=20 at Week 6
• Change From Baseline in Generalized Anxiety Disorder-7 (GAD-7) Total Score at Week 6
• Change From Baseline in Patient Health Questionnaire (PHQ-9) Total Score at Weeks 2 and 4
• Change From Baseline in HDRS-17 Total Score at Weeks 2 and 4
• Number of Participants With Treatment-emergent Adverse Events (TEAEs) as a Measure of Safety and Tolerability

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is continuous: HDRS-17 is a numeric scale, and the reported result is a mean change. A mean provides a summary of the group’s central value, but it does not show the spread of individual participant changes. Participants can have outcomes that differ substantially even when the group mean is similar. The arm-level summaries are least-squares means, which are model-based averages; the record does not give enough model detail to explain the exact covariate adjustment or estimation procedure used to obtain them.

What does the sponsor’s repeated-measures method do?

The sponsor reports a mixed model for repeated measures, commonly abbreviated MMRM. In general, repeated-measures methods analyze outcome observations collected at multiple assessment times while accounting for the fact that observations from the same participant are related. A mixed model can estimate treatment-group contrasts across time using the observed repeated measurements, subject to the model and its assumptions. The registry reports the method and the week 6 contrast, but details such as the covariance structure, included visits, covariates, and missing-data assumptions are not reported in the registry record. Those details matter for reproducing and fully assessing a model-based estimate.

The sponsor’s reported contrast is a least-squares mean difference. In general, a least-squares mean is an estimated group mean from a statistical model, rather than simply an arithmetic average of the raw observed values. The reported contrast is the active-treatment estimate relative to placebo. Its negative sign corresponds to a lower estimated change in the active-treatment arm, given the arm order and reported values. The registry’s reported confidence interval and p-value accompany this model-based contrast.

How does the simple re-calculation differ?

The re-calculation uses the posted arm-level summaries to form an unadjusted mean difference and an approximate interval and p-value. It is a simple comparison, rather than a reproduction of the sponsor’s MMRM. The arm-level means and standard errors are available, but the original participant-level outcome data and full model specifications are not. The approximate pooled standard deviation used for standardized effect calculations is derived from summary information, rather than being a direct analysis of participant-level observations. Therefore, the re-calculation is useful as a transparent check on the broad scale and uncertainty of the contrast, but it should not replace the sponsor’s reported model as the trial’s own analysis.

The re-calculated p-value is unadjusted. It does not account for testing multiple outcomes, choosing among analyses, or other features that could affect the overall interpretation. No adjustment is applied in this simple calculation, and the record does not report a multiplicity procedure for the primary and secondary analyses. The re-calculated interval is also not identified as the interval from the sponsor’s model; the two estimates arise from different analysis approaches and should not be treated as interchangeable.

What does uncertainty mean in this setting?

A confidence interval is a range of values that reflects sampling uncertainty under the method used to calculate it. In general, a wider interval indicates less precision, while a narrower interval indicates greater precision, all else being equal. An interval spanning zero includes a no-difference value, but it also includes nonzero values on either side. It does not prove that the true effect is exactly zero, nor does it prove that an effect exists. Interpretation depends on the interval’s width, the estimate, the outcome’s clinical context, and the credibility of the model assumptions.

The sponsor reports an 80% confidence interval for its MMRM estimate. The confidence level for the simple re-calculated interval is not specified in the posted analysis details. The primary analysis has no reported sponsor sample-size calculation or design assumptions in the registry record. Those omissions limit the ability to evaluate whether the study was planned around a particular effect size or how the sponsor intended to handle the full set of analyses.

Why does the analysis population matter?

The primary population is described as an enriched analysis set. It includes randomized participants who received at least one dose and met the specified baseline HDRS-17 conditions: less than 25 percent improvement in score from screening to baseline and a baseline total score of at least 18. This definition focuses the primary result on participants meeting those criteria. It also means that the result should not be casually generalized to a broader population without considering how the criteria affect applicability. The registry does not report whether additional populations were analyzed for the primary outcome or how results from any such analyses compare.

In general, missing outcome data can affect a treatment comparison when the availability of measurements is related to outcomes or treatment assignment. Mixed models can use available repeated observations under assumptions about missingness, but the validity of the estimate depends on those assumptions and the model specification. The registry does not report the amount or pattern of missing primary outcome data, the reasons for missingness, or sensitivity analyses. Without those details, the reader cannot judge how robust the result is to alternative assumptions about unobserved week 6 scores.

11. Confidence Intervals and Precision

The sponsor’s MMRM estimate is -0.61 HDRS-17 units, with an 80% confidence interval from -1.76 to 0.55. The interval includes zero and extends to values on both sides of it. It therefore does not rule out no between-group difference at the stated confidence level, and it also leaves room for a difference favoring either arm. The point estimate alone should not be read without this uncertainty range.

The simple unadjusted re-calculation gives a mean difference of -0.6, with an interval from -2.402 to 1.202. This interval also crosses zero and is wider than the sponsor’s reported interval, although the two are not identical analyses and the confidence level for the re-calculated interval is not specified in the posted details. A comparison of their widths is not a substitute for understanding the model and assumptions behind each calculation.

In general, a confidence interval describes the range of effect estimates reasonably compatible with the observed data under a particular statistical procedure. Precision concerns the range of plausible values, not whether a result is clinically important. The registry does not report a clinically important difference threshold for HDRS-17, so it is not possible to label the interval’s possible values as clinically meaningful or trivial using a trial-specific standard. The reported interval also pertains to the defined enriched analysis population and week 6 endpoint; it does not establish precision for other populations or timeframes.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size figures are planning illustrations expressed as participants per arm. They are not total event counts. The stated illustration uses a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It considers effects equal to the stated fraction of the observed effect. The trial’s own original design assumptions, including any original sample-size justification, are not reported in the registry record.

The 80% power column describes the planned number of participants per arm that the illustration estimates would be needed to have an 80% chance of detecting the specified effect under the stated assumptions, if that effect and model assumptions held. The 90% power column uses a higher target chance of detecting that effect and consequently calls for more participants per arm. These are design concepts for planning a future study, not descriptions of what happened to participants in this trial.

The rows that plan for a smaller fraction of the observed effect require more participants, because smaller differences are harder to distinguish from random variation. The displayed calculations use the observed effect as their starting point, so they should not be treated as a validated recommendation for a future trial. In particular, they do not incorporate any unreported design details or clinical judgment about which effect would be important to detect. This is not observed power: it is a prospective planning illustration based on the posted estimate and stated assumptions.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.600; pooled standard deviation σ = 6.498.
2. n = 2 × (1.96 + 0.842)² × 6.498² / -0.600² = 1,841.0, rounded up to 1,841 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.6                      # observed difference in means
sigma <- 6.49769376336129                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(4080752)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 1,841 (80% power), 2,465 (90% power)
 75% of observed effect: n per arm = 3,273 (80% power), 4,382 (90% power)
 50% of observed effect: n per arm = 7,364 (80% power), 9,859 (90% power)
power.t.test: 1842 
Simulated power at n = 1,841 per arm: 0.801 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor’s primary analysis is the MMRM result: a least-squares mean difference of -0.61, with an 80% confidence interval from -1.76 to 0.55 and p-value of 0.249. The simple re-calculation from the posted summary statistics estimates a difference of -0.6, with an interval from -2.402 to 1.202 and unadjusted p-value of 0.514. The point estimates are close in magnitude, while the intervals and p-values differ because the calculations are not the same analysis.

The re-calculation is an unadjusted summary-statistic comparison; the sponsor reports a repeated-measures model. Differences in modeling and uncertainty estimation can produce different intervals and p-values even when point estimates are similar. The registry does not give enough MMRM specification detail to reproduce the sponsor’s result independently. The registry marks no discrepancy between the posted results and the re-calculation, so the two should be presented as different analyses rather than as evidence that one has been flagged as inconsistent with the other. The sponsor’s reported analysis is the trial’s own stated analysis; the re-calculation is a supplementary, simple check and should not be mistaken for the prespecified analysis.

15. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study evaluates multiple outcomes, timepoints, subgroups, or statistical comparisons. Each additional analysis creates another opportunity for a result to appear unusual by chance. In general, a prespecified multiplicity strategy can help control the overall chance of false-positive findings across a defined family of tests. The registry lists multiple secondary outcomes and assessment times, but a multiplicity adjustment or hierarchy for interpreting them is not reported in the registry record. The unadjusted secondary re-calculations should therefore be treated as descriptive rather than as independent confirmatory evidence.

The registry identifies one reported primary MMRM analysis and gives its estimate, 80% confidence interval, and p-value. Details of the broader statistical analysis plan, including whether there were other planned primary analyses, how hypotheses were ordered, and how any multiplicity was addressed, are not reported in the registry record. It is also not reported whether interim analyses were planned or conducted. No assumption should be made about these aspects of the protocol.

The primary analysis population is defined as an enriched analysis set: randomized participants who received at least one dose and met the baseline HDRS-17 criteria. This is a specific analysis population, not necessarily an intention-to-treat population as that term is commonly used. The registry does not report enough detail to determine how participants without a week 6 measurement were treated in the sponsor’s MMRM, what missing-data assumptions were used, or whether sensitivity analyses were conducted. The number and reasons for missing measurements are not reported in the registry record.

These omissions matter because treatment-effect estimates can depend on who is included, how incomplete outcome data are handled, and how multiple comparisons are interpreted. They do not establish that the analysis was inappropriate; they limit what can be independently assessed from the registry record. The reported result should be understood in light of its stated enriched population and the analysis details that are available, without inferring unreported procedures.

16. 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 2% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports serious adverse event figures for the safety groups: 0 serious events among 112 participants at risk in the placebo group and 0 among 110 participants at risk in the JNJ-61393215 135 mg group. Deaths are listed as 0 in both groups. The registry’s list of top serious event terms is empty. These are the serious-event figures recorded for the groups and should be read with their stated at-risk counts.

The record also lists other adverse events for 12 participants at risk in the placebo group and 30 participants at risk in the active-treatment group. Those figures concern other adverse events, not the serious-event count. They should not be conflated with serious adverse events, and the registry summary does not provide event-level detail or a breakdown by type for these other events.

These counts alone do not establish comparative safety or rule out uncommon harms. The registry record does not provide further context about event definitions, severity, timing, duration, or attribution in the posted safety summary. Safety interpretation should remain limited to the categories and counts reported.

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

The primary result is an estimated comparison of week 6 HDRS-17 change between adjunctive JNJ-61393215 and adjunctive placebo in the defined enriched analysis population. The sponsor’s estimate is -0.61, with an 80% confidence interval from -1.76 to 0.55. The interval includes zero, so the reported estimate does not exclude no between-group difference under the stated analysis. The simple re-calculation also yields an interval spanning zero. Together, these results indicate uncertainty about the size and direction of the between-group difference in this study.

The average HDRS-17 change was negative in both groups. Because higher HDRS-17 scores represent greater depression severity, negative change corresponds to lower scores at follow-up than at baseline on average. This is a description of the observed group summaries; it does not establish that the study drug caused the changes. Participants in both arms continued standard antidepressant treatment, and the comparison addresses the added treatment against adjunctive placebo in that context.

The result does not establish that the treatments are equivalent. An interval that includes zero can still include nonzero effects, and the registry does not report a prespecified equivalence margin or a clinically important difference threshold. Nor does the result determine what might occur at other doses, with different background treatment, in a broader population, or beyond week 6. The primary analysis population required treatment exposure and particular baseline HDRS-17 characteristics, so generalization beyond that population requires caution.

The registry’s safety summary records no serious adverse events or deaths in either listed group, while listing other adverse events separately. Those summary counts do not provide a complete safety assessment. The registry record also does not report detailed missing-data handling, a multiplicity procedure, or a full statistical analysis plan. The most defensible interpretation is therefore bounded: the posted primary estimate does not demonstrate a clear between-group separation, and the available registry entries leave uncertainty about precision, generalizability, and the broader set of outcomes.

18. Why This Trial Matters Statistically

This trial illustrates why a treatment comparison should be read through its endpoint, analysis population, and uncertainty interval rather than through the direction of a point estimate alone. The active-treatment estimate is slightly more negative than the placebo estimate, but the reported confidence interval includes zero. A directional estimate is not, by itself, evidence of a reliably separated effect. The interval makes the uncertainty visible and prevents a point estimate from being treated as a definitive conclusion.

It also illustrates how the same clinical question can be analyzed in different ways. The sponsor reports an MMRM estimate, while a simple re-calculation based on arm summaries produces an unadjusted estimate and interval. Their point estimates are similar, but the uncertainty calculations differ. Knowing which result comes from the trial’s own reported model and which is a supplementary summary-statistic calculation is important for transparent interpretation.

The defined enriched analysis set matters for applicability. Its baseline and treatment-exposure criteria describe the population to which the primary result most directly pertains. The registry’s additional anxiety, depression, subgroup, and safety outcomes broaden the questions considered, but the lack of a reported multiplicity strategy means secondary findings deserve more cautious weight. Finally, the planning illustrations show how sample-size needs depend on the effect a future study aims to detect; they are not evidence of the design assumptions or power of this completed trial. These distinctions help separate what the record reports from what remains uncertain.

19. 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 registry record does not provide the full statistical analysis plan or sufficient MMRM specification to reproduce the sponsor’s primary estimate. Details such as covariates, covariance structure, handling of repeated visits, and missing-data assumptions are not reported in the registry record. The amount and pattern of missing primary outcome data and any sensitivity analyses are also not reported, limiting assessment of robustness.

The primary outcome population is an enriched analysis set requiring at least one dose and specific baseline HDRS-17 criteria. That population definition narrows the direct scope of the primary result. The registry does not report a comparison of this result with an analysis of all randomized participants, so the influence of the population definition cannot be assessed from the record.

Although the registry lists multiple secondary outcomes, detailed numerical results are not reported for every listed outcome, and sponsor analyses for the secondary outcomes are not reported in the registry record. A multiplicity procedure is not reported. The primary endpoint is at week 6; longer-term primary outcomes are not reported in the registry record. The registry also does not report a clinically important difference threshold for HDRS-17, making clinical interpretation of the estimated magnitude less specific.

The safety summary gives serious and other adverse event counts, but does not provide further event-level detail in the listed results. The registry does not report the original sample-size justification or detailed allocation and masking procedures. These are limits on what can be evaluated from this record; they do not establish that particular methods were or were not used.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study of JNJ-61393215 in the Treatment of Depression — NCT04080752.
• Registry record last updated 2025-04-29; status last verified 2025-04.
• Results first posted 2022-09-29.
• 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.

23. Record Summary

NCT04080752 is a completed phase 2 randomized, double-blind, parallel-group, placebo-controlled study of adjunctive JNJ-61393215 in adults with major depressive disorder with anxious distress and a suboptimal response to standard antidepressants. The registry lists enrollment of 222 and study dates of 2019-09-17 to primary completion on 2021-09-02.

The primary endpoint was change in HDRS-17 total score from baseline to week 6. The sponsor’s MMRM estimate was -0.61, with an 80% confidence interval from -1.76 to 0.55 and p-value of 0.249. The interval includes zero. The simple unadjusted re-calculation is similar in direction and also has an interval spanning zero, but it is not the sponsor’s model-based analysis. The registry’s primary analysis population was an enriched set defined by treatment exposure and baseline HDRS-17 criteria. The record reports no serious adverse events or deaths in either safety group, while listing other adverse events separately.