Psilocybin-assisted Group Therapy for Demoralization in Long-term AIDS Survivors: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Psilocybin-assisted Group Therapy for Demoralization in Long-term AIDS Survivors (NCT02950467), a na phase 1 study. The primary outcome is Number of Participants Who Experienced Treatment-related Adverse Events as Assessed by NIH Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0.

2. Clinical Question

These features shape what can be learned from the record. A single-group study can describe events observed during treatment and follow-up, and it can examine changes in measured outcomes over time if those results are reported. Without a concurrent comparator, it cannot establish how those observations differ from what would have happened without the intervention or under another form of care. The registry record does not report an analysis comparing outcomes with an external or historical control.

The primary endpoint is safety-focused rather than a direct test of whether demoralization changed. The secondary outcome list indicates that the investigators planned to assess several psychological measures at end of treatment and at follow-up, but the registry record does not report results for those outcomes. Consequently, the clinical question documented in the available record is narrower than a comparative treatment-effect question: it concerns treatment-related adverse events in participants receiving the combined intervention, with additional planned measures of psychological and group-related outcomes.

3. Trial Design

This completed study is recorded as Phase 1, with a single-group model and no allocation scheme. The registry lists enrollment of 30 and describes one intervention group receiving group therapy plus psilocybin. Because no concurrent control group is specified, the design is not a randomized comparison. The registry record does not report a protocol-based sample-size justification or a statistical analysis plan.

The intervention combined modified brief Supportive-Expressive Group Therapy with one oral psilocybin administration in a clinical setting. The therapy was described as ten twice-weekly sessions. The registry identifies the study as unmasked. In a single-group study, this means the record does not describe a masking procedure that would conceal treatment assignment from participants or study personnel; there is no separate treatment assignment to conceal between study arms.

The primary outcome was the number of participants with treatment-related adverse events, using the NIH Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0. Its stated timeframe was enrollment to 3-month follow up, described as about 5 months. The outcome description says adverse events were assessed at every study visit by patient interview. During medication visits, assessment also included vital-sign monitoring, participant self-report, and events observed by clinicians.

The listed secondary outcomes include changes in demoralization, complicated grief, and depressive symptoms at end of treatment and at 3-month follow-up, as well as a pre-drug versus post-drug comparison of average Group Questionnaire subscale scores. The registry lists 25 outcome measures overall, but does not report results for these secondary outcomes in the registry record for this analysis. It also lists 0 analyses. The study is recorded as completed, with a start date of 2018-01-05 and primary completion on 2019-12-31. Further details about participant flow, protocol deviations, and analysis populations are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Before assignment: 91 study candidates were screened over the phone, of which 37 were eligible for in-person enrollment evaluations, of which 30 attended an in-person enrollment evaluation and were consented to the study. 18 candidates were found to be eligible for the study, all of whom enrolled in the trial and initiated treatment.

Open-label Treatment

3-month Follow-up

5. Baseline Characteristics

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

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Who Experienced Treatment-related Adverse Events as Assessed by NIH Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events, Version 2.0, measured over Enrollment to 3-month follow up, about 5 months.

The primary endpoint is a participant count: the number of participants who experienced treatment-related adverse events during enrollment through 3-month follow up, described as about 5 months. The registry identifies the NIH Division of AIDS severity grading table as the assessment framework. Adverse events were assessed at study visits through participant interviews, with additional vital-sign monitoring, self-report, and clinician observation during medication visits.

A count of affected participants is useful in an early-phase study because it describes how many people in the observed group had events considered treatment-related. It is a safety measure, not a direct measure of change in demoralization or another psychological outcome. A participant count also differs from an event count: one participant may experience multiple events, while the endpoint title refers to participants who experienced an event.

The record separately reports serious and other adverse-event summaries, but those summaries do not establish the primary endpoint count. In particular, the serious-event summary does not by itself indicate whether an event was judged treatment-related. The registry record does not report the number of participants meeting the primary endpoint definition, nor does it report a confidence interval or a formal analysis for that endpoint. Therefore the posted serious and other event figures should be read as safety summaries, not as a substitute for the stated primary outcome result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate? In a single-group study, outcomes are observed among participants who receive the study intervention. Such a design can describe the frequency of recorded events and the distribution of measured outcomes in that group. If repeated measurements are reported, changes over time can also be described. Those within-group observations do not supply the counterfactual outcome: what the same participants would have experienced over the same period under a different treatment or without the intervention. A concurrent comparison group is commonly used to estimate that contrast, but this study is recorded as single-group and has no allocation to a comparator.

That distinction matters for causal interpretation. A change after treatment can reflect the intervention, but it can also reflect the natural course of symptoms, other care, expectations, measurement conditions, or changes in who remains available for assessment. Without a comparative group and a reported analysis, the separate contributions cannot be determined from this record. The registry does not report a statistical plan that would describe how such issues were intended to be addressed.

What does a participant count represent?

The primary outcome is defined in terms of the number of participants who experienced treatment-related adverse events. This is a count of people meeting the outcome definition, rather than necessarily a count of every event. Counting participants can make the proportion of the observed group with at least one qualifying event understandable, but repeated events within a participant do not create additional affected participants under that definition. The registry record does not report the primary endpoint result, so the count of participants with treatment-related adverse events cannot be read from the posted serious-event summary alone.

For binary outcomes, the underlying observation for each person can be represented as whether the person met the event definition during the specified period. A summary count can then be interpreted only alongside its denominator and the precise event definition. If an interval estimate is reported, it describes uncertainty in the estimated event frequency under the chosen statistical method. No interval estimate for the primary endpoint is reported in the registry record. General statistical principle: smaller samples usually yield less precise estimates than larger samples, and a count without an uncertainty estimate gives limited information about how precisely the underlying event frequency has been estimated.

Why distinguish treatment-related from serious events?

“Serious” and “treatment-related” describe different aspects of an adverse event. Seriousness concerns the event's classification under safety criteria; relatedness concerns whether it is judged to be associated with the intervention. An event may be serious without being judged treatment-related, and an event considered related need not be serious. Thus, the posted count of participants with serious adverse events cannot be substituted for the primary endpoint, which is explicitly about treatment-related events. The record gives a separate serious-event summary and does not report the primary treatment-related count.

The assessment procedures described in the registry included interviews at every study visit and, during medication visits, vital-sign monitoring, self-report, and clinician observation. Multiple sources can help identify events, but the record does not provide enough detail to assess the completeness of event capture, how judgments of relatedness were made, or whether assessors followed a prespecified adjudication process. Those details are not reported in the registry record.

What do the planning illustrations mean?

General statistical principle: power calculations are planning tools that describe how a proposed study might perform under specified assumptions. They are not a measure of what the completed study actually achieved, and they are not a substitute for its observed results. The described planning framework uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with effects framed as fractions of an observed effect. It states that results for non-time-to-event outcomes are expressed as participants per arm, while time-to-event calculations use a total event count. Those are planning assumptions, not features of the actual single-group design, which has no two-arm allocation.

In particular, a planning illustration based on an observed effect does not show that the trial had a specified probability of detecting an effect after completion. It is not “observed power.” The registry record does not report the trial's own sample-size justification. No new sample-size calculation or inference can be made from the design details alone, and the planning assumptions should not be mistaken for a randomized design or a reported analysis.

How should multiplicity and uncertainty be considered?

The registry lists multiple secondary outcomes, including several measures assessed at more than one time point. When many outcomes or time points are examined, the chance of at least one apparently notable result can increase if each is assessed separately without adjustment. General statistical practice may address this by prespecifying a primary comparison, defining a multiplicity strategy, or emphasizing estimation and uncertainty rather than isolated significance tests. The registry record does not report a multiplicity strategy, the statistical analysis plan, or outcome-specific analysis details. Therefore no adjustment or unadjusted inference should be assumed.

Missingness also matters: an outcome measured at follow-up may be unavailable for some participants. The registry record does not report participant-level completion, reasons for missing measurements, imputation procedures, or analysis populations for the psychological outcomes. Without those details, it is not possible to assess whether missing observations could affect any reported change estimate. In this record, results for those secondary measures are not reported, so no estimate can be interpreted for missing-data sensitivity.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Group Therapy Plus Psilocybin")
n      <- c(18)
events <- c(18)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Group Therapy Plus Psilocybin  18  18  100.0  81.5  100.0  82.4  100.0  82.4  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 25 outcome measures overall, including several secondary measures at end of treatment and at 3-month follow-up. It does not report a multiplicity strategy explaining how the number of outcomes or assessment times was considered when interpreting statistical tests. The registry record also lists 0 analyses, and it does not provide a statistical analysis plan. It is therefore not possible to determine whether any testing was adjusted, whether outcomes were prioritized beyond the stated primary endpoint, or how any exploratory results were intended to be distinguished from confirmatory results.

Analysis populations are also not described in the registry record for this analysis. The record does not report whether analyses were based on all enrolled participants, those who received the intervention, or those with available outcome measurements. Enrollment was 30, while the adverse-event summaries list 18 at risk; the registry record does not explain the difference. No conclusion about reasons for the different denominators should be inferred.

For the secondary psychological measures, participant flow at each assessment, missing-data handling, and sensitivity analyses are not reported in the registry record. General statistical principle: missing observations can affect an estimate if the people with missing results differ systematically from those whose results are observed. Without the relevant counts and assumptions, the direction and size of any such effect cannot be assessed. Since the secondary results themselves are not reported, no change estimate or missing-data analysis can be evaluated.

The primary treatment-related adverse-event result is also not reported. The posted serious and other event counts do not resolve this omission because they are separate safety summaries and do not identify the endpoint's treatment-related classification.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

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

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: renal cell carcinoma (5.6%), pneumothorax (5.6%), stimulant-induced psychosis (5.6%), suicide attempt (5.6%), cholecystitis (5.6%).

The registry's adverse-event summary lists 3 participants with serious adverse events among 18 at risk, and 18 participants with other adverse events among 18 at risk. It also lists 0 deaths. These figures describe the posted serious and other event categories; they do not state that each event was judged related to psilocybin or group therapy. The registry lists renal cell carcinoma, pneumothorax, stimulant-induced psychosis, suicide attempt, and cholecystitis among the serious-event terms, each with a listed value of 5.6%.

These categories should not be collapsed into the primary endpoint. The primary endpoint concerns participants who experienced treatment-related adverse events, whereas the available figures concern serious and other adverse events. Seriousness and relatedness are different classifications, so the serious-event count cannot be used as the number of participants with treatment-related events.

The safety denominator is 18, compared with enrollment of 30. The registry record does not explain this difference. The event figures should therefore be read with their stated denominator and should not be generalized to participants outside that safety summary without further information. The record also does not provide event-level details in the registry record for this analysis, such as timing, duration, severity grades, or relatedness judgments for each listed term. The listed percentages and terms alone do not establish causality.

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

The registry record documents a completed Phase 1, single-group study combining group therapy and one oral psilocybin administration for long-term AIDS survivors. Its stated primary endpoint focused on treatment-related adverse events during enrollment to 3-month follow up, described as about 5 months. The posted safety summary records serious and other adverse events in the group with a safety denominator of 18, as well as 0 deaths. These observations describe the events recorded in that summary; they do not by themselves establish whether events were caused by the intervention or how participants' symptoms changed.

The record does not report the primary treatment-related adverse-event count. It also does not report results for the secondary measures of demoralization, grief, depression, or group functioning. Consequently, the listed design and safety details do not permit an estimate of change in those psychological outcomes or a statistical assessment of the primary endpoint. The completed status is a registry status, not a substitute for outcome estimates.

Because there was no control group, the study cannot show how outcomes would compare with another treatment or with no study intervention. It also cannot separate the contribution of group therapy from the contribution of psilocybin. General statistical principle: causal claims require a design and analysis that address alternative explanations for observed outcomes; a single-group observation alone does not provide a concurrent treatment contrast.

The results should therefore be read as a description of a small early-phase study's design and posted event summaries, not as a comparative estimate of treatment effect or a complete account of safety. The record does not report uncertainty intervals for the primary endpoint, detailed participant flow, or analysis populations. Those omissions limit the precision and scope of conclusions that can be drawn from the registry information.

14. Why This Trial Matters Statistically

This study is statistically notable because its primary endpoint is a safety count in an early-phase, single-group design, while the intervention combines a drug with a structured group therapy. That setup calls for careful separation of descriptive safety monitoring from comparative treatment-effect estimation. Event counts can characterize what was recorded among participants in the study, but without a comparator they cannot establish how those event patterns differ from another treatment or from the absence of the intervention.

The record also illustrates why outcome definitions matter. Its primary endpoint refers to participants with treatment-related adverse events, while the posted adverse-event summary distinguishes serious and other events. Seriousness does not establish treatment relatedness, so the available safety figures should not be treated as the primary endpoint result. Matching the result to the precise endpoint definition is essential before drawing a statistical interpretation.

The enrollment and safety denominators differ: enrollment is 30, while the safety summaries list 18 at risk. The registry record does not explain that difference. This makes clear why participant flow and analysis populations are important parts of interpreting even basic counts. Without them, the scope of the safety summary cannot be fully assessed.

Finally, the registry lists psychological secondary outcomes, but does not report their results or the statistical analysis plan. Multiple outcomes and follow-up times raise questions about prespecification, multiplicity, missing data, and the distinction between exploratory and confirmatory analyses. Those questions cannot be resolved from the available record. Statistically, the study's relevance lies in the safety questions it set out to address and in the need to interpret its posted counts within the design and endpoint definitions, rather than treating a single-group record as a comparative test.

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.

The registry record describes a single-group study with no comparator, so it cannot support a direct estimate of how outcomes differ from another treatment or from no intervention. The intervention includes both group therapy and psilocybin; the design does not separate their individual contributions. These design features limit causal interpretation regardless of how carefully outcomes were measured.

The record does not report a result for the stated primary endpoint of treatment-related adverse events. The serious and other adverse-event summaries are not equivalent to that endpoint because the summary does not specify treatment relatedness. The record's safety denominator is 18, while enrollment is 30, and no explanation for this difference is reported. Participant flow and reasons for inclusion in the safety summary are not reported in the registry record.

Although several secondary outcomes are listed, their results are not reported in the registry record for this analysis. The record does not report the statistical analysis plan, multiplicity handling, missing-data methods, analysis populations, or uncertainty intervals. It also does not provide enough information to assess the completeness of adverse-event capture or the method used to determine relatedness. The record's completed status does not resolve these reporting gaps.

These limitations are specific to interpretation of this study record: the intervention is combined, the design has no control group, the event summaries use a denominator smaller than the stated enrollment, and the primary and secondary results are not reported. Findings from the available summaries should therefore be confined to describing the posted counts and design rather than extending them to causal or comparative conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Psilocybin-assisted Group Therapy for Demoralization in Long-term AIDS Survivors — NCT02950467.
• Registry record last updated 2021-01-07; status last verified 2020-12.
• Results first posted 2021-01-07.
• 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.

19. Record Summary

The registry identifies a completed Phase 1 study of psilocybin-assisted group therapy for demoralization in long-term AIDS survivors. It records enrollment of 30, a single-group design, and no allocation to a comparator. The intervention combined modified brief Supportive-Expressive Group Therapy, described as ten twice-weekly sessions, with one oral psilocybin administration in a clinical setting.

The primary outcome concerned the number of participants experiencing treatment-related adverse events during enrollment to 3-month follow up, described as about 5 months. The posted safety summaries list 3 participants with serious adverse events among 18 at risk, 18 with other adverse events among 18 at risk, and 0 deaths. A primary treatment-related event count is not reported. The registry also lists secondary measures of demoralization, grief, depression, and group functioning, but their results are not reported in the registry record.

The record does not report a statistical analysis plan, multiplicity approach, missing-data methods, or analysis populations. The design supports descriptive interpretation of the posted safety summaries, but does not provide a randomized comparative estimate.