Individual Differences in Drug Response: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Individual Differences in Drug Response (NCT03809546), a randomized early/phase 1 study. The primary outcome is Change From Baseline in Profile of Mood States (POMS).

2. Clinical Question

3. Trial Design

The registry classifies this as an early-phase 1, randomized, quadruple-masked, parallel trial. Its status is completed, and the recorded enrollment is 60. The listed arms are placebo, 7.5 mg THC, and 15 mg THC. The adverse-event records list 20 participants at risk in each arm, but the registry does not provide a fuller account of the allocation process or the analyzed population.

The study dates are recorded as a start on 2018-11-06 and primary completion on 2021-06-01. The brief summary describes acute oral THC, placebo, and testing at two menstrual-cycle phases. It says cycle phase was assessed using serum estradiol and progesterone analyses and self-reported responses, and describes administration in a double-blind and counterbalanced design. The registry's classification of the model as parallel and the summary's description of counterbalancing are both part of the record; how those descriptions relate to the actual assignment and dosing sequence is not reported in the registry record.

The listed interventions are dronabinol and dextrose. The registry record does not specify the capsule schedule, the interval between doses, or how menstrual-cycle phase was incorporated into the randomization or analysis. It also does not report a protocol rationale for the enrollment target, a sample-size justification, or whether interim analyses were planned. The stated hypothesis concerns associations between estradiol and several types of response, while the registered primary outcome focuses on mood measured with POMS.

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

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 Change From Baseline in Profile of Mood States (POMS), measured over Difference from baseline (time 0 or pre-capsule) to post-capsule (120 min).

The registered primary endpoint is change from baseline in Profile of Mood States (POMS), measured in units on a scale. The stated timeframe is the difference from the pre-capsule assessment, identified as time 0, to the post-capsule assessment at 120 min. POMS is a self-rating instrument intended to measure positive and negative mood states. The registry describes a 30-item form with six mood factors: Tension-Anxiety, Depression-Ejection, Anger-Hostility, Vigor-Activity, Fatigue-Inertia, and Confusion-Bewilderment.

The record says scoring can yield a global score from 0 to 120 or individual domain scores, with subscale scores from 0-20; lower scores indicate a better mood state. A continuous endpoint can retain gradations in a measured score rather than reducing observations to categories. Reporting a mean and standard deviation can describe the average change and the spread of changes in a group. The registry identifies the endpoint parameter as a mean and its dispersion as a standard deviation, but does not report group means, standard deviations, or a treatment contrast.

POMS is relevant to the study's stated interest in subjective response. It does not, on its own, measure the cardiac or neuroendocrine responses also mentioned in the research rationale. The operational details for calculating the change score, including the handling of item-level or domain-level scores, are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the trial design tell readers?

Random allocation is a design method intended to distribute known and unknown participant characteristics across assigned groups, reducing systematic differences at assignment. It does not guarantee that the groups will be identical, particularly in a small study, and it cannot replace a clear account of how outcomes were analyzed. The registry identifies the allocation as randomized but does not report the sequence-generation method, concealment procedures, or any stratification factors.

Masking is intended to limit the influence of knowledge about assignment on participant experiences, care, or assessment. The registry labels masking quadruple, and the brief summary describes the study as double-blind. The exact roles covered by each label and the procedures used to preserve masking are not reported in the registry record. The parallel classification ordinarily means participants are assigned to one group rather than crossing through all groups, but the summary's counterbalanced description raises a design detail that cannot be resolved from the record alone.

How should a continuous endpoint be understood?

POMS change is registered as a continuous outcome summarized by a mean and standard deviation. The mean describes the group's average change, while the standard deviation describes variation among individual changes. These quantities answer different questions: a mean characterizes the central average, and a standard deviation describes dispersion around that average. Neither indicates how precisely a group mean or a contrast between groups has been estimated. A confidence interval would communicate uncertainty in an estimate; no such interval or estimate is reported for the primary endpoint.

Change from baseline uses each participant's post-capsule score relative to their pre-capsule score. A comparison of average changes between assigned groups would address whether average change differed across those groups, subject to the analysis choices and assumptions. The registry does not report the group-level values, the contrast, or the statistical method used to make that comparison. It also does not say whether the change was calculated for the global POMS score, a domain, or another scoring specification.

What does the record say about statistical planning?

The record does not report a statistical analysis plan, a model, covariate adjustments, or a sample-size justification. The registry's stated planning assumptions describe a general sample-size illustration based on an observed effect: two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. These are planning assumptions, not proof that the trial used those procedures for its outcome analysis. They do not establish observed power, and the record does not list a completed analysis from which such planning values could be interpreted.

More generally, a sample-size calculation asks how much information a future study might need under stated assumptions. Its result depends on the assumed effect and variability, the chosen significance level, allocation, and the power target. It is not a measure of the probability that a particular study has found a real effect. In this record, no endpoint analysis or observed effect is posted, so the planning assumptions do not supply a result for the present trial.

What can be said about statistical uncertainty?

When an estimate and its standard error are available, a confidence interval provides a range of values compatible with the data under the method's assumptions. A narrow interval generally indicates greater precision than a wide interval, while the interval's location helps describe the direction and scale of the estimate. A p-value, when reported, addresses compatibility of data with a specified null model; it does not measure the size or importance of an effect. Neither a p-value nor a confidence interval is reported for the primary POMS endpoint in this registry record.

With no outcome estimates, readers cannot assess dispersion, precision, or whether an observed contrast might be compatible with a range of effects. The record also does not identify how repeated measurements, menstrual-cycle phase, estradiol levels, or potential correlations among outcomes were handled in analysis. Those omissions prevent a fuller statistical interpretation of the stated research question.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists one primary outcome measure, but that endpoint has several possible scoring domains and time points in its description. The record also indicates that the primary outcome has several categories or time points and is not reduced to one comparison. No outcome analysis is listed. This means there is no single posted contrast to interpret, and the registry record does not identify which POMS score or comparison would serve as the principal inferential test.

Multiplicity arises when several outcomes, time points, subgroups, doses, or comparisons are examined. If multiple tests are considered, the chance of at least one apparently unusual result can increase unless the analysis plan accounts for those tests. Common approaches include defining a hierarchy of outcomes, adjusting inference, or treating secondary analyses as exploratory. These are general statistical options; the record does not report whether any such strategy was specified or used. The existence of multiple domains or measurement occasions does not establish that all were analyzed.

Missing-data methods and analysis populations are not reported in the registry record. It is not stated whether all randomized participants were included in the primary analysis, how incomplete POMS assessments were handled, or whether exclusions or imputation were used. These details matter because missingness can affect the meaning and reliability of a comparison, depending on why observations are absent and how the analysis handles them. The record does not provide enough information to assess that issue.

The registry reports zero analyses for the outcome and no endpoint results. That should be interpreted as an absence of posted analyses in the record, not as evidence that no analysis occurred outside it. Without a prespecified analysis description and results, readers cannot evaluate multiplicity control, missing-data assumptions, or consistency between the planned and reported analyses.

11. 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.

For placebo, 7.5 mg THC, and 15 mg THC, the registry lists 20 participants at risk for serious adverse events and 20 at risk for other adverse events in each arm. The recorded affected counts are 0 for serious adverse events and 0 for other adverse events in each arm. Deaths are recorded as 0 in each arm, and no serious-event terms are listed.

These entries describe the adverse-event counts recorded in the registry, not a complete account of how safety was monitored. The record does not report event definitions, ascertainment procedures, severity grading, exposure time, follow-up completeness, or whether the counts include all events or only events meeting a specified reporting threshold. Zero recorded events does not establish that an intervention has no risk, and it does not show that risks are equivalent across groups. The figures should be interpreted as registry entries within the information available, not as a definitive safety comparison.

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

The record establishes that a randomized, quadruple-masked, parallel early-phase study was registered as completed, with placebo and two THC dose arms. It identifies change in POMS as the primary outcome and describes a measurement from pre-capsule assessment to post-capsule assessment at 120 min. The brief summary places this endpoint within a broader question about estradiol and physiological and subjective response.

What the record does not establish is the observed mood response in any arm or a difference between arms. It does not provide an estimated effect, confidence interval, p-value, or analysis method for the primary endpoint. It therefore cannot support a claim about the direction, size, or precision of a POMS contrast. It also does not report whether estradiol levels were associated with outcome variation, whether cycle phase modified response, or whether cardiac and neuroendocrine outcomes supported the broader hypothesis.

Statistical evidence and clinical interpretation are related but distinct. A numerical difference, if available, would need to be considered alongside its uncertainty, the scoring scale, the study design, and the relevance of the measured change. A result from a small early-phase study would also need cautious interpretation in light of the population studied and the registry's reporting detail. Here, the endpoint results themselves are not reported, so those assessments cannot be made.

The adverse-event entries show zero reported events in the listed categories for each arm, but the details necessary to judge the completeness and scope of safety monitoring are absent. These counts do not establish an absence of risk. Similarly, the completed status indicates the trial's registry status, not that all planned analyses or results have been made available.

The most defensible reading is therefore descriptive: the record identifies the trial's intended comparison and measurement, but leaves the central outcome and analysis questions unanswered. It neither demonstrates a treatment effect nor demonstrates that no effect exists. Further interpretation would require posted outcome estimates and the statistical and operational details needed to understand them.

13. Why This Trial Matters Statistically

This trial is statistically notable for asking an individual-differences question rather than only asking whether average responses differ by assigned dose. The brief summary focuses on whether circulating estradiol is associated with response to THC, and whether physiological response is associated with subjective response. Such questions involve relationships among measured characteristics and outcomes, and may require analyses that account for repeated observations, cycle phase, and correlations among response measures. The registry record does not report how those analyses were planned or performed.

The study also illustrates why a registered endpoint and an available result are different kinds of information. POMS change is specified with a measurement timeframe and scale description, but no outcome estimates or comparisons are posted. Without those estimates, readers cannot assess effect size or precision, regardless of the design labels or the stated hypothesis. The record's completed status alone does not fill that gap.

For clinical researchers, the record highlights the value of reporting the exact outcome definition, the analysis population, missing-data handling, and the planned contrasts among dose and placebo groups. Those details are especially relevant when an endpoint has multiple domains or measurement occasions, and when the research question includes biological associations as well as group comparisons. Clear reporting would allow readers to distinguish the primary treatment comparison from exploratory analyses and to judge uncertainty.

The adverse-event entries also demonstrate the limits of interpreting event counts without information about surveillance and follow-up. A zero count is a reported observation, not a complete statistical characterization of safety. More broadly, transparent outcome and methods reporting is necessary for evaluating what a study contributes, beyond its design and rationale.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting this trial is that the registry record does not report results for the registered primary outcome. It gives no POMS mean change, standard deviation, treatment contrast, confidence interval, or p-value. Consequently, the intended comparison cannot be evaluated statistically from the posted record.

The record does not specify which POMS score was analyzed, despite describing a global score and individual domains. It also does not explain how change scores were calculated or how the multiple measurement occasions and domains were handled. The stated timeframe identifies the baseline and post-capsule assessment, but the record does not provide endpoint values at either assessment or analysis details.

Information about the study population is limited to the summary's description of healthy females. Eligibility criteria, participant characteristics, exclusions, and analysis populations are not reported in the registry record. The registry classifies the design as parallel, while the brief summary refers to counterbalanced dosing; the practical relationship between these descriptions is not explained. Details about dose sequence, cycle-phase assignment, and whether the same participants contributed measurements across conditions are also not reported.

The registry does not provide a statistical analysis plan, missing-data procedures, multiplicity strategy, sample-size justification, or details of interim analyses. It also does not report the collection and follow-up procedures needed to fully interpret the adverse-event counts. These limitations restrict evaluation of both the intended inference and the completeness of the posted safety information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Individual Differences in Drug Response — NCT03809546.
• Registry record last updated 2024-07-03; status last verified 2024-01.
• Results first posted 2024-07-03.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT03809546 is a completed early-phase 1 randomized, quadruple-masked, parallel trial sponsored by the University of Chicago. The registry records enrollment of 60 and lists placebo, 7.5 mg THC, and 15 mg THC arms. The stated research question concerns estradiol and response to THC in healthy females, while the registered primary outcome is change from baseline in POMS from pre-capsule assessment to 120 min after capsule administration.

The record describes POMS as a mood measure and identifies mean and standard deviation as the outcome summary. It does not report primary outcome estimates, an analysis comparing groups, or results for the broader estradiol hypothesis. Adverse-event entries list zero serious events, zero other events, and zero deaths in each arm. Analysis methods, missing-data handling, and safety-ascertainment details are not reported in the registry record.