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 Maximizing Analgesia to Reduce Pain in Knee Osteoarthritis (NCT03098563), a randomized phase 2 study. The primary outcome is Largest Change From Baseline on Clinical Pain Rating.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03098563 |
| Phase | Phase 2 |
| Condition | Knee Osteoarthritis |
| Allocation | Randomized |
| Design model | Crossover |
| Masking | Triple |
| Enrollment | 58 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Johns Hopkins University |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned people with chronic knee osteoarthritis pain. The registry record lists an enrollment of 58. Further eligibility details and characteristics of the enrolled participants are not reported in the registry record.
Intervention
Participants received blinded study medication during outpatient study sessions. The registry describes a within-subject design: session procedures were intended to be identical, with the medications administered on a given study day as the planned change. The listed medication conditions included hydromorphone, dronabinol, and placebo, alone or in combination.
Comparator
The registry lists four conditions: Placebo + Placebo, Hydromorphone + Placebo, Dronabinol + Placebo, and Hydromorphone + Dronabinol. The specific randomized order, washout arrangements, and details of how each participant experienced the conditions are not reported in the registry record.
Primary question
The study planned to measure whether blinded study medications changed clinical pain ratings during an 8 hour study session. The endpoint was the largest change from baseline on a 0-100 pain rating scale, with higher scores indicating a worse outcome. The registry record does not report a single numerical comparison for this endpoint, so it does not establish the size or precision of a difference between the medication conditions.
3. Trial Design
This was a phase 2, randomized, triple-masked crossover study sponsored by Johns Hopkins University. The registry lists an enrollment of 58 and the condition as knee osteoarthritis. The study began on 2017-11-01, reached primary completion on 2023-11-17, and is listed as completed.
A crossover design evaluates more than one condition within the same participant. General statistical context: when measurements from the same person are compared across conditions, the analysis can account for the fact that those observations are related. Such a design can reduce the influence of stable differences between participants, but it also makes the order and timing of conditions important. The registry describes the study as within-subject and says session procedures were intended to be identical, with the medications administered that day as the change. The randomized sequence and any washout details are not reported in the registry record.
The four listed medication conditions were Placebo + Placebo, Hydromorphone + Placebo, Dronabinol + Placebo, and Hydromorphone + Dronabinol. Study sessions were outpatient visits lasting approximately 8 hours. The listed procedures included standardized pain testing, brief physical functioning testing, blood draws, questionnaires, and cognitive testing at multiple points over a visit. The registry lists blinded study medication as the intervention and describes masking as triple. Which roles were masked and the exact masking procedures are not reported in the registry record.
The registry summary says the research evaluated whether combining medications approved individually, but not yet approved for combination treatment, could reduce pain. It does not report the protocol’s rationale for the enrollment target, the planned sequence generation method, or the statistical analysis plan in enough detail to reconstruct the primary comparison.
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: Experimental Session 1 is a safety session and completed first. The remaining sessions were completed in triple blinded randomized order.
Experimental Session 1
| Stage | Hydromorphone+Placebo | Placebo+Placebo | Dronabinol + Placebo | Hydromorphone + Dronabinol |
|---|---|---|---|---|
| STARTED | 58 | 0 | 0 | 0 |
| COMPLETED | 58 | 0 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Experimental Sessions 2-4
| Stage | Hydromorphone+Placebo | Placebo+Placebo | Dronabinol + Placebo | Hydromorphone + Dronabinol |
|---|---|---|---|---|
| STARTED | 0 | 58 | 0 | 0 |
| COMPLETED | 0 | 58 | 0 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Experimental Sessions 2-4
| Stage | Hydromorphone+Placebo | Placebo+Placebo | Dronabinol + Placebo | Hydromorphone + Dronabinol |
|---|---|---|---|---|
| STARTED | 0 | 0 | 58 | 0 |
| COMPLETED | 0 | 0 | 58 | 0 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
Experimental Sessions 2-4
| Stage | Hydromorphone+Placebo | Placebo+Placebo | Dronabinol + Placebo | Hydromorphone + Dronabinol |
|---|---|---|---|---|
| STARTED | 0 | 0 | 0 | 58 |
| COMPLETED | 0 | 0 | 0 | 58 |
| NOT COMPLETED | 0 | 0 | 0 | 0 |
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 | Overall |
|---|---|---|
| Participants analysed | 58 | |
| Age, Continuous | years | 62.34 (SD 6.57) |
| Sex: Female, Male: Female | Participants | 36 |
| Sex: Female, Male: Male | Participants | 22 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 57 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 22 |
| Race (NIH/OMB): White | Participants | 31 |
| Race (NIH/OMB): More than one race | Participants | 2 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 2 |
| Region of Enrollment: United States | Participants | 58 |
6. Primary Endpoint
The registry lists the primary outcome as Largest Change From Baseline on Clinical Pain Rating, measured over 8 hour study session.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | score on a scale |
| Endpoint classification | Continuous Endpoint |
The primary endpoint was the largest change from baseline in clinical pain rating during an 8 hour study session. Ratings used a 0-100 pain rating scale, and the registry states that a higher score indicates a worse outcome. The listed summary measure was the mean, with standard deviation as the measure of dispersion.
Using the largest change over a session is one way to focus on the most pronounced recorded change during that observation period rather than on a single measurement time. General statistical context: pain can vary during a visit, so repeated measurements can describe how ratings change over time. A summary based on the largest change retains a particular feature of those repeated measurements, but it does not by itself describe the full trajectory, the timing of the largest change, or how ratings behaved at other points.
The registry record does not define the direction used to calculate change from baseline, report the time point at which the largest change occurred, or give outcome values by medication condition. It also notes that the primary outcome has several categories or time points and was not reduced to one comparison. Consequently, the endpoint definition can be described, but a numerical contrast and its uncertainty cannot be interpreted from the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized crossover study with four medication conditions and a continuous pain-rating endpoint. It does not report a single primary-outcome comparison or numerical results for the largest change from baseline. There is therefore no posted estimate, confidence interval, or p-value for that endpoint in the record. The magnitude and precision of any contrast between conditions cannot be assessed from the listed endpoint information.
The outcome description identifies a mean and standard deviation as the summary measures. These alone would not identify the treatment contrast unless the corresponding condition-level results and the analysis method were also available. In a crossover study, observations from the same participant are related. A valid contrast generally needs to reflect that within-person structure, rather than treating measurements from one person as independent observations. The exact model or test used is not reported in the registry record.
The registry’s note that the primary outcome has several categories or time points and was not reduced to one comparison matters for interpretation. A collection of measurements may support multiple possible contrasts, such as comparisons at different points or across different categories. Without a designated estimate and analysis details, readers cannot determine which comparison was intended to answer the primary question or how uncertainty was handled across the possible comparisons.
There is no basis in the registry record to characterize the size of an observed pain change, its direction, or whether it was statistically distinguishable from a comparator. The absence of a reported numerical result is not evidence that the conditions had identical results, nor is it evidence that any condition produced a particular effect. The registry record also does not report a clinically important threshold for interpreting score changes.
The safety entries list zero serious adverse events and zero deaths in each of the four conditions. They also list other adverse events for each condition. These counts are descriptive entries, not estimates of comparative safety. The record does not provide the event terms, timing, severity breakdown, or an analysis comparing conditions. The crossover setting also means that condition-level counts should not automatically be read as independent groups of different people.
Overall, the record establishes the study question, design, endpoint definition, and listed safety counts, but not a numerical primary efficacy result. General statistical context: estimates are most informative when reported with a measure of uncertainty, such as a confidence interval. A confidence interval describes a range of values compatible with the data and analysis assumptions; no such interval for the primary endpoint is reported in the registry record.
9. Statistical Methods Explained
What does randomization contribute?
The registry describes the study as randomized. General statistical context: randomization assigns study conditions according to a chance-based process, which can reduce systematic differences in how conditions are assigned. In a crossover trial, randomization may concern the order in which participants receive conditions. The registry record does not report the sequence-generation method, allocation procedures, or whether the listed conditions were assigned in a particular order. Randomization should therefore be noted as a design feature, without assuming details about its implementation.
How does a crossover design affect analysis?
The record describes a within-subject study in which session procedures were intended to remain the same while the medications administered each study day changed. General statistical context: measurements from one participant across conditions are correlated. An analysis can use within-person contrasts and account for that correlation. Treating all condition measurements as unrelated would discard information about which observations came from the same person and could misstate uncertainty. The statistical model, handling of repeated observations, and assumptions about period or sequence effects are not reported in the registry record. Details about washout periods and carryover are also not reported in the registry record, so their adequacy cannot be assessed.
What does a mean and standard deviation describe?
The primary outcome is listed as a mean with standard deviation. General statistical context: the mean describes a distribution’s average, while the standard deviation describes how dispersed observations are around that average. Neither quantity alone is a comparison between conditions. A treatment contrast requires condition-specific results and a specified method for comparing them. The registry record does not report the primary outcome values needed to describe such a contrast.
Why do repeated time points matter?
The pain rating scale was used during an 8 hour study session, and the endpoint was the largest change from baseline over the session. The record notes that the primary outcome has several categories or time points and was not reduced to one comparison. General statistical context: repeated measurements can be analyzed in several ways, including by comparing a selected summary or by modeling the measurements over time. The choice affects the question being answered. Selecting the largest change emphasizes the most extreme recorded change; it does not provide a complete account of the trajectory. The registry record does not specify which time points contributed to each category or how the multiple measurements were handled in the analysis.
What is multiplicity, and why can it matter?
General statistical context: multiplicity arises when several outcomes, time points, groups, or contrasts are examined. When many statistical tests are conducted, the chance of at least one apparently unusual result can increase if each test is judged on its own. Researchers may define one primary comparison in advance or use an approach that accounts for multiple comparisons. The registry record does not report a multiplicity adjustment or a complete analysis plan. Its note that the outcome was not reduced to one comparison makes it especially important not to treat any single contrast as the definitive primary result without further documentation.
What can a confidence interval tell readers?
General statistical context: a confidence interval communicates uncertainty around an estimated contrast. A narrower interval indicates greater precision under the model’s assumptions; a wider interval indicates less precision. It does not by itself establish clinical importance, and its interpretation depends on the analysis being appropriate. No confidence interval for the primary pain endpoint is reported in the registry record, so precision cannot be evaluated from the record.
What does the sample-size illustration mean?
The record describes a planning illustration based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. General statistical context: such an illustration explores how a hypothetical future study’s size could relate to an effect selected for detection and a chosen power target. It is not the number of participants observed in this trial and is not observed power. The illustration is not the trial’s own design justification. The registry record does not report the original sample-size rationale or the assumptions used when planning the completed study.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists one primary outcome measure and one analysis, but also states that the primary outcome has several categories or time points and was not reduced to one comparison. Those statements do not identify a single contrast that can be interpreted as the primary result. The registry record does not report whether multiple comparisons were adjusted, whether a hierarchy of comparisons was prespecified, or which result was considered primary in the analysis.
Missing-data handling is not reported in the registry record. The record does not say how incomplete pain-rating sessions, missed measurements, or participants without complete observations were handled. It also does not report the number of participants contributing data to the primary endpoint or a comparison of those included and not included in the analysis. These omissions limit assessment of whether the analyzed observations represent the enrolled participants.
The analysis population is not reported in the registry record. It is therefore unclear whether the primary analysis included all randomized participants, only those completing specified sessions, or another defined group. General statistical context: in a crossover study, missing measurements can affect condition comparisons differently depending on which sessions are incomplete. The analysis population and missing-data approach are needed to judge how such incomplete observations influence an estimate.
The registry does not report interim analyses, stopping rules, or further details of the statistical plan. Without those details, the handling of multiple measurements and the path from recorded observations to a primary estimate cannot be reconstructed.
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 |
|---|---|---|---|
| Placebo + Placebo | 0 | 58 | 0.0% |
| Hydromorphone + Placebo | 0 | 58 | 0.0% |
| Dronabinol + Placebo | 0 | 58 | 0.0% |
| Hydromorphone + Dronabinol | 0 | 58 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Placebo + Placebo | 0 of 58 |
| Hydromorphone + Placebo | 0 of 58 |
| Dronabinol + Placebo | 0 of 58 |
| Hydromorphone + Dronabinol | 0 of 58 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Placebo + Placebo | 15 of 58 |
| Hydromorphone + Placebo | 10 of 58 |
| Dronabinol + Placebo | 13 of 58 |
| Hydromorphone + Dronabinol | 21 of 58 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo + Placebo | Hydromorphone + Placebo | Dronabinol + Placebo | Hydromorphone + Dronabinol |
|---|---|---|---|---|---|
| Nausea | Gastrointestinal disorders | 2 of 58 | 1 of 58 | 1 of 58 | 2 of 58 |
| Hypotensive | Cardiac disorders | 1 of 58 | 1 of 58 | 1 of 58 | 1 of 58 |
| Clumsy | Nervous system disorders | 1 of 58 | 1 of 58 | 1 of 58 | 1 of 58 |
| Dizziness | Nervous system disorders | 1 of 58 | 1 of 58 | 1 of 58 | 1 of 58 |
| Drowsiness | Nervous system disorders | 1 of 58 | 1 of 58 | 1 of 58 | 1 of 58 |
| Light Headed | Nervous system disorders | 1 of 58 | 1 of 58 | 0 of 58 | 2 of 58 |
| Headache | Blood and lymphatic system disorders | 1 of 58 | 1 of 58 | 0 of 58 | 1 of 58 |
| Vomiting | Gastrointestinal disorders | 0 of 58 | 1 of 58 | 1 of 58 | 1 of 58 |
| Blurred Vision | Nervous system disorders | 0 of 58 | 0 of 58 | 1 of 58 | 2 of 58 |
| Difficulty Concentrating | Nervous system disorders | 1 of 58 | 1 of 58 | 0 of 58 | 1 of 58 |
The registry lists four medication conditions. Each has 58 participants at risk for serious adverse events, with zero serious adverse events listed. The record also lists zero deaths in each condition. Under other adverse events, the listed counts are 15 for Placebo + Placebo, 10 for Hydromorphone + Placebo, 13 for Dronabinol + Placebo, and 21 for Hydromorphone + Dronabinol.
These entries are descriptive counts. They do not establish that one condition is safer than another, and they do not show whether an event was caused by a study medication. The registry record does not list the terms for these other adverse events, their severity, timing, duration, or the number of events per affected participant. It also does not describe how participants who experienced events were handled across subsequent sessions.
Because this was a crossover study, the condition entries should not be interpreted as four independent groups of different participants without further information. The registry record lists 58 at risk under each condition, but does not explain the counting method or whether the same people contributed to more than one condition. Zero serious events in the listed entries is not proof that serious events are impossible; it is the recorded count in this study.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a phase 2 randomized, triple-masked crossover study evaluated blinded medication conditions in people with chronic knee osteoarthritis pain. It identifies the primary endpoint as the largest change from baseline in clinical pain rating during an 8 hour session and states that higher scores indicate a worse outcome. These details describe the research question and measurement, not the result.
The record does not report a single numerical comparison for the primary endpoint. No condition-specific endpoint means, contrast, confidence interval, or p-value is available in the record. It is not possible to say from these details how much ratings changed, whether the medication conditions differed, or how precise any difference was. The absence of a reported estimate should not be read as evidence of no effect, just as the study’s design does not establish that a medication condition changed pain ratings.
General statistical context: a difference in a measured score is not automatically meaningful to patients. Interpretation would depend on the direction and size of the estimate, its uncertainty, the measurement properties of the scale, and a clinically meaningful threshold. The registry record does not report such a threshold or the primary-outcome result needed to make that assessment.
The safety entries report zero serious adverse events and zero deaths in each listed condition, alongside other adverse-event counts. Those entries do not provide a complete safety profile or a comparative analysis. Missing event descriptions and analysis details limit what can be concluded about the nature and distribution of events.
The record also describes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. General statistical context: planning calculations are hypothetical design tools, not a measure of the probability that a completed study’s finding is true. The illustration is not observed power and does not replace the missing primary-outcome estimate.
13. Why This Trial Matters Statistically
This study raises several statistical issues that are common in clinical trials. First, it uses a crossover design, with sessions described as within-subject and the medications administered on each study day as the intended change. Such designs can compare conditions within the same person, but interpretation depends on the relationship among repeated measurements and on how sequence, period, and possible carryover are handled. The registry record does not report those analysis details.
Second, the endpoint summarizes the largest change from baseline over an 8 hour session while pain ratings were measured at multiple points. A maximum-type summary answers a focused question about the most pronounced change, but it does not represent the entire time course. The registry note that the outcome has several categories or time points and was not reduced to one comparison leaves the target contrast unclear. This illustrates why a clearly defined primary comparison is important for interpreting results and uncertainty.
Third, the registry lists serious and other adverse-event counts by condition, but these descriptive entries do not supply event terms or comparative estimates. Safety interpretation requires attention to how events were counted and to the fact that participants may contribute observations under more than one condition in a crossover study.
Finally, the record separates a planning illustration from the trial’s original design justification. General statistical context: sample-size calculations depend on assumptions about the effect to detect, variability, allocation, and the analysis. A planning illustration can explore those assumptions, but it cannot substitute for an outcome estimate or serve as observed power. The missing endpoint comparison, analysis details, and uncertainty measures are central to understanding what the trial’s posted information can support.
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 study is that the registry record does not report a single primary-outcome comparison or numerical endpoint results. Without condition-level results and an estimated contrast, the magnitude, direction, and precision of any difference cannot be assessed. The record’s note that the outcome has several categories or time points and was not reduced to one comparison adds uncertainty about which contrast was intended to answer the primary question.
The registry does not report the statistical model, the treatment of repeated measurements, or how the within-subject structure was reflected in the analysis. Randomization and triple masking are listed, but sequence generation, masking procedures, washout arrangements, and handling of possible period or carryover effects are not reported in the registry record. These details are important for evaluating a crossover study.
The analysis population and missing-data procedures are not reported in the registry record. The record does not state how many participants contributed endpoint data, how incomplete sessions were handled, or whether analyses followed the randomized assignments. It also does not give participant characteristics or detailed eligibility criteria, limiting assessment of whom the results would describe even if outcome estimates were available.
Safety reporting is limited to counts by condition. The registry does not report other adverse-event terms, event severity, timing, or comparative analyses. The record also does not report a clinically meaningful threshold for changes on the pain-rating scale. Consequently, neither clinical importance nor a comprehensive benefit-risk interpretation can be drawn from these entries alone.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Maximizing Analgesia to Reduce Pain in Knee Osteoarthritis — NCT03098563.
- Registry record last updated 2024-12-11; status last verified 2024-11.
- Results first posted 2024-12-11.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT03098563 is a completed phase 2 randomized, triple-masked crossover study sponsored by Johns Hopkins University. It enrolled 58 people and studied knee osteoarthritis. The registry lists four medication conditions: Placebo + Placebo, Hydromorphone + Placebo, Dronabinol + Placebo, and Hydromorphone + Dronabinol. The study began on 2017-11-01 and reached primary completion on 2023-11-17.
The primary endpoint was the largest change from baseline in clinical pain rating during an 8 hour session, measured on a 0-100 scale where higher scores indicate a worse outcome. The registry record does not report a single primary-outcome comparison or numerical results. It lists zero serious adverse events and zero deaths in each condition, along with other adverse-event counts. Details of the analysis population, missing-data handling, and statistical model are not reported in the registry record.