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 Tenofovir Rectal Douche to Prevent HIV Transmission Among Adolescents (ATN DREAM) (NCT04686279), a na phase 1 study. The primary outcome is Tenofovir Diphosphate (TFV-DP) Concentration.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04686279 |
| Phase | Phase 1 |
| Condition | HIV/AIDS, HIV Prevention |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 8 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of Pennsylvania |
| Results posted | Yes |
2. Clinical Question
Population
Adolescent men enrolled in ATN DREAM. The registry reports an enrollment of 8 participants.
Intervention
A single dose of tenofovir medicated douche, followed by post-dose observations and sampling.
Comparator
There is no separate comparator group. The study is recorded as single-group, with allocation listed as not applicable.
Primary question
What tenofovir diphosphate concentrations are measured in colonic tissue cells after the douche, at the sampling schedules specified in the registry?
The study is an early phase investigation of safety, pharmacokinetics, pharmacodynamics, acceptability, and desirability. Its stated overall goal is to inform the design of an extended safety study of an on-demand douche intended for use in an outpatient pre-RAI context. The primary endpoint is a concentration measurement, not a comparison of HIV acquisition between treatment groups.
The posted primary outcome describes colonic tissue cell tenofovir diphosphate concentrations at 1 hour, 24 hours, or 72 hours after administration. Participants assigned to each sampling schedule are included in the outcome description. The registry does not report the concentration results themselves, so the question can be stated from the endpoint definition, but the magnitude and spread of the observed concentrations cannot be assessed from the registry record.
The study can therefore describe measurements collected after a single dose in the enrolled group. Without a separate comparator and without reported HIV acquisition outcomes, it does not estimate a comparative preventive effect. Its stated purpose is early-stage characterization and informing future study design, not a definitive test of clinical protection.
3. Trial Design
ATN DREAM is registered as a phase 1, open-label, single-group study. The allocation field is listed as not applicable, masking is none, and the study model is single group. The registry reports an enrollment of 8 participants. The sponsor is the University of Pennsylvania. The study start is listed as 2021-04-01, primary completion as 2022-11-30, and status as completed.
Participants completed a baseline sampling session and then received a single dose of study product. The arm description states that post-dose observations and data collection followed at 1, 6, 24, and 72 hours. It describes a sparse pharmacokinetic sampling design that includes plasma and peripheral blood mononuclear cells. The primary outcome description separately specifies colonic tissue cell tenofovir diphosphate concentrations at 1 hour, 24 hours, or 72 hours, according to each participant’s sampling schedule.
Because the design has one group and no randomized allocation, it is not a randomized comparison. Measurements can describe concentrations and recorded safety events among participants who received the douche, but they cannot isolate a treatment effect relative to a concurrent control group. Open-label status means masking was not used; the registry does not report additional procedures to limit measurement or reporting bias.
The registry identifies three outcome measures, but the primary outcome is the one detailed in the record available for this analysis. The number of analyses is listed as zero. A fuller protocol, detailed analysis plan, and explanations for the number of participants enrolled are not reported in the registry record. The design is consistent with an early-phase investigation, but the registry does not report a sample-size justification or a planned inferential framework.
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 | TFV Medicated Douche |
|---|---|
| STARTED | 8 |
| COMPLETED | 8 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: Participants assigned to each sampling schedule (1 hr, 24hr, 72 hr) are included below.
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 | TFV Medicated Douche |
|---|---|---|
| Participants analysed | 8 | |
| Age, Continuous | Years | 21 (18 to 24) |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 8 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 0 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 3 |
| Race (NIH/OMB): White | Participants | 5 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: United States | participants | 8 |
| Body Mass Index | kg/m^2 | 27.0 (22.7 to 36.2) |
6. Primary Endpoint
The registry lists the primary outcome as Tenofovir Diphosphate (TFV-DP) Concentration, measured over At 1 hour, 24 hours, or 72 hours after the TFV douche administration.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | femtomole/million cells |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the concentration of tenofovir diphosphate (TFV-DP) in colonic tissue cells, expressed in femtomole/million cells. The registry specifies that the summary measure is the median and that dispersion is described using the full range. Samples are associated with 1 hour, 24 hours, or 72 hours after the single douche administration, depending on the participant’s sampling schedule.
As a general statistical explanation, a concentration endpoint can characterize whether and how much a drug-related compound is measurable in a sampled tissue after administration. Tissue measurements are relevant to a study concerned with a product intended for rectal use, while scheduled measurements can describe how concentrations vary across the observed post-dose sampling times. A median gives a measure of the center of the observed values that is less influenced by an extreme value than a mean can be. A full range communicates the lowest and highest observations, although it does not show how values are distributed between those limits.
The registry record does not report the actual medians or ranges. It therefore does not permit a reader to judge the observed concentration levels, their variability, or differences across sampling schedules. Nor does this endpoint itself measure HIV acquisition or establish a protective concentration threshold; such a threshold is not reported in the registry record. The endpoint is a pharmacologic measurement, not a direct clinical outcome.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies a pharmacologic outcome: median colonic tissue cell TFV-DP concentration, with the full range, at the specified post-dose sampling times. However, the values for this endpoint are not reported in the registry record. This means the central concentration and the extent of observed variability cannot be interpreted from the posted results. The endpoint definition alone does not reveal whether concentrations were measurable or how they differed across sampling schedules.
The study enrolled 8 participants and used a single-group, open-label design. Its observations can describe what was recorded after one dose in this group, but there is no separate control group against which to compare those observations. The design therefore does not support a randomized estimate of the effect of the douche relative to another intervention or to no intervention. The registry does not report an HIV acquisition outcome as the primary endpoint, and the concentration measure should not be treated as proof of prevention.
The registry lists no analyses. It does not report an inferential estimate, a confidence interval, or a p-value for the primary endpoint. A confidence interval, as a general statistical concept, represents uncertainty around an estimate under specified assumptions; without a reported interval or sufficient individual-level data, the uncertainty around these concentration results cannot be assessed. The median and full-range format would be descriptive even if values were posted, and should not be confused with an adjusted treatment comparison.
The safety record lists 8 participants at risk for serious adverse events and 0 affected. For other adverse events, 8 were at risk and 3 were affected. These are participant counts in the registry record. No serious adverse-event terms are listed. The record does not supply event descriptions, severity categories for the other events, timing, attribution, or a detailed account of how events were collected. Consequently, the counts should not be extended into claims about cause or clinical importance.
Overall, the registry supports a narrow reading: a small early-phase group received a single dose, and safety counts and a concentration endpoint were specified. The concentration values are not reported in the registry record, and no comparative analysis is posted. The study’s stated role is to inform the design of further safety work. The available record does not establish a preventive effect, quantify uncertainty around pharmacologic measurements, or resolve how the findings might apply beyond the enrolled group.
9. Statistical Methods Explained
The primary endpoint is reported as a median with a full range. As a general statistical explanation, the median is the middle value after observations are ordered. It describes the center without requiring values to be symmetrically distributed. That can be useful when a small group may have skewed measurements or isolated extreme values. The full range gives the minimum and maximum observed values. It conveys the span, but not how many observations lie near either endpoint or whether values cluster within the interval. The registry record does not report the actual median or range for TFV-DP concentrations.
What does sparse sampling mean?
The arm description calls the pharmacokinetic design sparse and lists post-dose collection at 1, 6, 24, and 72 hours. The primary outcome description focuses on colonic tissue cell measurements at 1 hour, 24 hours, or 72 hours, according to participants’ sampling schedules. In general, sparse sampling means that a participant contributes measurements at selected time points rather than necessarily at every scheduled time. This can reduce the amount of sampling required per participant, but it also means that the pattern over time is assembled from observations taken under the study’s sampling scheme. The record does not report individual schedules or individual-level measurements, so the degree to which time patterns can be evaluated is unclear.
Why distinguish the endpoint from a treatment comparison?
A concentration measurement describes a pharmacologic quantity in a specified sample. A treatment comparison instead estimates how an outcome differs between groups or conditions. This study is single group, with allocation listed as not applicable and no separate comparator. Its concentration endpoint can therefore be described among participants after administration, but there is no concurrent control group for estimating a comparative treatment effect. This design distinction is important even when the measurement itself is objective: a numerical concentration does not by itself show what would have occurred without the intervention.
What does the absence of an analysis mean?
The registry lists zero analyses. It does not report a statistical analysis plan, a model for the concentration data, an inferential estimate, or a confidence interval. As a general explanation, an analysis plan clarifies which observations will be summarized, how missing measurements are handled, and which estimates will answer the study questions. A confidence interval can convey uncertainty around an estimate, while a statistical test can assess compatibility with a specified null hypothesis under its assumptions. Neither should be inferred from a descriptive endpoint definition. Since the concentration values and analyses are not reported in the registry record, no estimate of statistical uncertainty can be reconstructed from the stated summary format alone.
How should planning illustrations be read?
The sample-size assumptions describe a planning illustration based on an observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. These are assumptions for a planning exercise, not a description of the actual single-group study design. The registry record does not report a sample-size justification for ATN DREAM. Any sample-size illustration is a planning aid and not observed power. It should not be read as evidence that the study had a particular probability of detecting an effect, nor as a retrospective measure of what the study established.
The planning assumptions refer to two arms, while the study design is single group and does not include a randomized comparison. That contrast means the illustration does not describe the allocation actually used in ATN DREAM. The underlying values needed to interpret particular planning scenarios are not reported in the registry record. General statistical principles cannot fill in missing study-specific estimates or establish which future design would be appropriate.
Why does over-dispersion matter in general?
Over-dispersion occurs when observed variability is greater than a statistical model expects. As a general concept, if a model understates variability, its uncertainty estimates may be too narrow and tests may appear more decisive than warranted. The registry does not report a model for the concentration endpoint or evidence that over-dispersion was assessed. The median and full range are descriptive summaries, not a model-based adjustment for extra variability.
In a small study, individual observations can have a substantial influence on summaries, and the range can be especially sensitive to extreme values. This is a general consideration, not a claim about the measurements in ATN DREAM: the registry does not report individual values. Reporting the full range alongside the median can make the spread more visible, but without the observations or a distributional display, the shape and consistency of the measurements remain unknown.
10. Multiplicity, Missing Data and Analysis Populations
The registry identifies three outcome measures, but the primary outcome description is the only one detailed in the record used for this analysis. The number of analyses is listed as zero. A statistical plan describing outcome hierarchy, planned contrasts, or adjustments for multiple testing is not reported in the registry record. It is therefore not possible to determine how the study planned to handle multiplicity or whether any particular outcome was prioritized for formal inference beyond its registry designation as primary.
As a general explanation, multiplicity arises when several outcomes, time points, or statistical comparisons are examined. Looking at many results can increase the chance that at least one appears unusual by chance. Strategies for addressing this depend on the scientific aims and analysis plan. No adjustment method or testing strategy is reported in the registry record, so none should be assumed. The primary endpoint’s several sampling times also do not establish that separate formal comparisons were planned.
The registry does not report missing-data counts, reasons for missingness, imputation, or rules for excluding observations. It is not possible to tell whether each participant contributed a primary endpoint measurement or how incomplete sampling was handled. The endpoint description says participants assigned to each sampling schedule are included, but does not give schedule-specific participant counts in the available record.
Similarly, an analysis population definition is not reported in the registry record. The enrolled group is stated as 8, but the record does not describe whether analyses used all enrolled participants, only those who received the dose, or only those with evaluable samples. No interim analysis plan is reported. These absences limit assessment of selective reporting, missingness, and the relationship between enrollment and the analyzed measurements.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| TFV Medicated Douche | 0 | 8 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| TFV Medicated Douche | 0 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| TFV Medicated Douche | 3 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | TFV Medicated Douche |
|---|---|---|
| Type I Diabetes | Metabolism and nutrition disorders | 2 of 8 |
| Nausea | Gastrointestinal disorders | 1 of 8 |
| Polyp | Gastrointestinal disorders | 1 of 8 |
The registry reports 8 participants at risk for serious adverse events and 0 affected. It reports 8 at risk for other adverse events and 3 affected. These are counts of participants recorded in the adverse-event fields, not a complete account of event types, timing, severity, or causality. The registry lists no serious adverse-event terms.
A count of 0 affected in this group means that the record lists no participants as having a serious adverse event. It does not establish that the risk of such events is absent in a broader population. As a general statistical point, a small group provides limited information about uncommon outcomes, and absence of a recorded event is not the same as proof that an event cannot occur.
The count of 3 affected for other adverse events does not identify what those events were or whether they were considered related to the study product. The registry record does not report the event descriptions or attribution. These counts should therefore be read as a brief safety summary, not as a detailed safety profile or comparative risk estimate. Because the study has no separate comparator, the counts cannot be used to compare event rates between treatment groups.
12. What the Result Does, and Does Not, Mean
The result definition shows what ATN DREAM set out to measure: TFV-DP concentration in colonic tissue cells after a single tenofovir douche dose, summarized by a median and full range at specified sampling times. The record also provides brief adverse-event counts for the enrolled group. Those details establish the type of early-phase information the study was designed to collect, but the primary concentration values are not reported in the registry record.
The record does not show the observed median concentrations or their range, so it cannot support a judgment about the amount or variability of TFV-DP in tissue. It also does not provide a comparative estimate, confidence interval, or p-value. With a single group and no separate comparator, any observed post-dose measurement would be descriptive rather than a randomized estimate of a treatment effect.
The endpoint is pharmacologic, not a direct measure of HIV acquisition. The study title and stated objective concern HIV prevention, but the primary outcome described in the record is a tissue concentration. The registry does not report that a particular concentration predicts protection or identify a protective threshold. Accordingly, the endpoint should not be interpreted as demonstrating prevention or lack of prevention.
The adverse-event summary records 0 participants affected by serious adverse events among 8 at risk, and 3 affected by other adverse events among 8 at risk. The record gives no event terms for serious events and no details about the other events. These counts provide limited descriptive safety information; they do not establish causation, comparative safety, or the frequency of uncommon outcomes outside this group.
The stated goal is to inform the design of an extended safety study. That is a development-stage purpose. The registry record does not report a sample-size justification, a detailed statistical plan, missing-data handling, or inferential analyses. The findings available in the record therefore cannot answer broader questions about efficacy, durability, comparative safety, or generalizability. They describe an early investigation and the limits of the information posted for it.
13. Why This Trial Matters Statistically
This study illustrates why the design and the endpoint must be read together. A tissue concentration can be relevant to understanding the pharmacology of a rectal product, but it is not interchangeable with a clinical outcome such as HIV acquisition. The distinction matters because a measurement may support further investigation without establishing that a preventive effect has occurred.
ATN DREAM is an early phase 1, open-label, single-group study with an enrollment of 8 participants. That structure is suited to collecting initial observations, but it does not create a randomized contrast. The lack of a comparator limits what can be attributed to the intervention rather than to other influences or background variation. The concentration outcome is also not numerically reported in the registry record, so its observed level and spread cannot be reviewed.
The record offers an example of how descriptive summaries and inferential conclusions differ. A median and full range describe observed values; they do not alone quantify uncertainty or establish a difference from another condition. The registry lists no analyses, and does not report a confidence interval, statistical test, or sample-size justification. A planning illustration based on assumptions is not the same as evidence generated by the study, nor is it observed power.
The safety fields likewise show the importance of careful interpretation. Counts of participants affected are useful descriptive information, but without event details, attribution, or a control group, they cannot establish comparative risks or explain the clinical meaning of each event. The available record is therefore most informative when treated as a description of an early study’s aims, design, and limited posted outcome information. It also makes clear why subsequent studies and more complete reporting would be needed to answer questions beyond initial pharmacologic and safety characterization.
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 the primary outcome is that the registry record defines the TFV-DP concentration endpoint but does not report its values. Without the medians and full ranges, readers cannot evaluate the observed concentrations, variability, or pattern across sampling schedules. Individual-level measurements and schedule-specific participant counts are also not reported in the record.
The design is single group and open label, with allocation listed as not applicable and no comparator. It cannot provide a randomized comparison. The enrollment of 8 participants also means the record describes a small early-phase group; the registry does not report a rationale for that enrollment or a sample-size justification. No efficacy endpoint measuring HIV acquisition is detailed as the primary outcome.
Important analysis details are not reported in the registry record, including a statistical analysis plan, definitions of analysis populations, missing-data handling, multiplicity procedures, and interim analyses. The number of analyses is listed as zero, and no inferential estimates or uncertainty intervals are reported. These omissions prevent assessment of how the outcome data were handled or how precisely any estimated concentration was measured.
The adverse-event information is limited to participant counts. Serious-event terms are not listed, and descriptions, severity details for other events, timing, and attribution are not reported. As a result, the safety fields cannot support a detailed assessment of event patterns or a comparison of risk.
Finally, the registry states an aim to inform an extended safety study, but does not provide protocol detail sufficient to evaluate broader design choices. The listed sampling schedule and sparse sampling description do not establish that every participant contributed measurements at every time point. These limitations confine interpretation to the stated study design and the information recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Tenofovir Rectal Douche to Prevent HIV Transmission Among Adolescents (ATN DREAM) — NCT04686279.
- Registry record last updated 2023-10-30; status last verified 2023-10.
- Results first posted 2023-10-30.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
ATN DREAM is a completed phase 1, open-label, single-group study sponsored by the University of Pennsylvania. The registry reports an enrollment of 8 and describes a single dose of tenofovir medicated douche, followed by post-dose observations. The primary endpoint is median colonic tissue cell TFV-DP concentration, with the full range, at 1 hour, 24 hours, or 72 hours according to sampling schedule.
The registry lists 0 participants affected by serious adverse events among 8 at risk and 3 affected by other adverse events among 8 at risk. No serious-event terms are listed. The actual primary concentration values, inferential analyses, detailed analysis plan, and sample-size justification are not reported in the registry record. The study is intended to inform further safety-study design; its posted information does not establish a comparative or preventive effect.