Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease (NCT01771731), a randomized phase 1, phase 2 study. The primary outcome is Pain Rating Using Visual Analog Scale at Day 1 and Day 5.

2. Clinical Question

The broader study objectives also included assessing short-term side effects during concomitant opioid and cannabinoid use, and examining short-term effects on markers of inflammation and disease progression. The registry summary states hypotheses about pain, opioid-related side effects, and those biological markers. These are stated aims, not evidence that an effect was observed.

The record identifies a randomized crossover study in which participants received both interventions. That design makes the comparison within participants rather than solely between separate groups. However, the posted results do not report numerical pain means, confidence intervals, or an inferential comparison. The registry record therefore does not establish the direction, size, or precision of a pain difference between the interventions.

3. Trial Design

The registry lists this study as Phase 1 and Phase 2, randomized, quadruple-masked, and crossover. Its title is Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease, and its official title is Cannabinoid-Based Therapy and Approaches to Quantify Pain in Sickle Cell Disease. The listed condition is sickle cell disease. The sponsor is the University of California, San Francisco.

The registry lists enrollment as 27. The study began in 2014-08, reached primary completion on 2017-05-12, and has a completed status. Those record entries describe the trial's registration and administrative status; they do not supply an outcome estimate or indicate how many participants contributed data to each analysis.

In a crossover design, each participant receives more than one intervention, so the participant can contribute observations under both conditions. Here, the primary-outcome population is explicitly described as all participants who received both interventions. The active and placebo schedules were the same: vaporized cigarette contents at 12pm on Day 1, three times daily on Days 2-4, and at 8am on Day 5. The active cigarette contents are described as 4.7% THC and 5.1% CBD; the placebo contents are described as 0% THC and 0% CBD.

Randomization and masking are recorded, but the registry record does not report the sequence-generation method, concealment details, or which roles were included in the quadruple masking. It also does not report the order assigned to each participant, a washout interval, or procedures for assessing whether masking was maintained. These details should not be inferred from the design labels alone.

The registry record does not report a statistical analysis plan or a completed primary-outcome analysis. In particular, it does not identify how the within-participant comparison accounted for repeated observations, period or sequence effects, or missing measurements. The existence of a crossover design identifies the broad structure of the comparison, but not the model or assumptions used to analyze it.

4. Participant Flow and Accounting

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

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All participants received both interventions.

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 Pain Rating Using Visual Analog Scale at Day 1 and Day 5, measured over Day 1 and Day 5.

The primary endpoint is a mean pain rating measured with a visual analog scale at Day 1 and Day 5. The record states that the scale ranges from 0-100 and that lower scores mean lower pain while higher scores mean higher pain. A visual analog scale represents a subjective symptom on a continuous scale, allowing changes in reported pain to be described numerically rather than only as categories.

Using a mean provides a summary of the observed ratings, while the stated 95% confidence interval is intended to express uncertainty around that summary. In general, a confidence interval conveys a range of values compatible with the data and the method used to calculate it; it is not a guarantee that the true value lies in that particular interval. Interpretation depends on the analysis population, the estimate, and the method used.

The registry specifies Day 1 and Day 5 as the measurement time points but does not give the actual mean ratings or confidence intervals. It also does not state in the results whether the primary comparison is a change from Day 1, an endpoint comparison at Day 5, or another contrast involving both time points. The posted outcome title alone does not resolve that analytical detail. Consequently, the endpoint definition explains what was intended to be measured, but the registry record does not provide a numerical estimate of the cannabis-placebo contrast.

VAS pain ratings are useful for examining symptom intensity over time, but they remain participant-reported measurements. Their interpretation depends on consistent collection, complete data, and a clearly defined comparison. Those collection and analysis details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry identifies a continuous primary outcome summarized as a mean with a 95% confidence interval. The design is randomized and crossover, and the listed analysis count is zero. No detailed statistical plan or primary-outcome model is reported in the registry record. The methods below explain general principles relevant to this type of study; they should not be read as a description of analyses that the investigators actually performed.

What does a mean summarize?

For a continuous measure such as a pain score, the mean is the arithmetic average of observed values in the analysis population. It provides a concise description of the center of those measurements, but by itself does not show how spread out the individual ratings are. A mean can also be affected by unusually high or low values. Interpretation therefore benefits from knowing the distribution, the number of observations contributing, and how missing measurements were handled. Those outcome details are not reported in the registry record.

What does a 95% confidence interval communicate?

In general, a confidence interval describes uncertainty around an estimated quantity under a specified statistical method and its assumptions. A narrower interval indicates greater precision than a wider interval for the same kind of estimate. An interval around a group mean is not automatically an interval for the difference between interventions. For a treatment comparison, the estimate and interval need to correspond to the contrast of interest. Although the endpoint lists a 95% confidence interval, the registry record does not provide the interval or specify the analysis used to calculate it.

Why does crossover structure matter?

In a crossover study, the same participant contributes data under multiple intervention conditions. Measurements from one participant tend to be related, so treating them as if they came from unrelated people can misrepresent uncertainty. General approaches account for within-participant correlation, for example through a paired analysis or a model that represents repeated observations. The appropriate method depends on the outcome schedule, sequence, assumptions, and missingness. The registry record does not report which approach was used.

Crossover studies can also be affected by time and sequence. A period effect occurs when outcomes change over time for reasons apart from the assigned intervention. A carryover effect occurs when an earlier intervention has effects that persist into a later period. Randomization can help balance factors, but does not remove the need to define and assess relevant design assumptions. The registry record does not report treatment order, a washout interval, or an analysis of period or carryover effects, so those features cannot be evaluated from the posted information.

What does masking contribute?

Masking is intended to reduce the influence of knowledge about assigned treatment on care, reporting, or assessment. The record labels the study quadruple-masked, but does not specify which participant, investigator, clinician, assessor, or other roles were masked, nor how masking was maintained. The label alone does not show whether participants or staff could distinguish the vaporized contents or whether masking was successful.

What should be considered for over-dispersion?

Over-dispersion is a general issue for count outcomes when the observed variability is greater than expected under a simple statistical model. It is especially relevant when modeling event counts or rates, rather than a continuous mean such as the stated pain score. If an analysis assumes less variability than the data contain, uncertainty can be understated. The registry record does not report a count-based model for the primary endpoint, and no model for secondary outcomes is specified; therefore, it is not possible to say whether over-dispersion was assessed or relevant to any analysis.

What do the sample-size assumptions mean?

The record describes planning illustrations based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It states that the effect to detect is a stated fraction of the observed effect. Such sample-size illustrations are planning calculations, not evidence about what the study actually detected, and they are never observed power. In a crossover trial, a planning calculation also depends on assumptions about within-participant variability and correlation; those assumptions are not reported in the registry record. The posted information does not establish that these illustrations were the investigators' original design justification.

What is missing from the analysis description?

The registry record does not report a statistical analysis plan, a primary-outcome model, an adjusted or unadjusted estimate, a p-value, or an analysis population beyond the statement that all participants received both interventions. It does not describe covariate adjustment, handling of incomplete repeated measurements, or any planned interim analysis. These omissions prevent readers from reconstructing the primary analysis or assessing whether its assumptions were met.

10. Multiplicity, Missing Data and Analysis Populations

The study summary describes several objectives: pain, short-term side effects associated with opioid use, and markers of inflammation and disease progression. The registry lists one outcome measure and does not list any analyses. The relationship between the stated objectives and a prespecified family of statistical tests is not reported in the registry record. It also does not say whether one outcome was designated as the sole confirmatory test or how multiplicity across outcomes, time points, or comparisons would be addressed.

Multiplicity matters in general when several hypotheses are tested, because interpreting each test independently can increase the chance of at least one false-positive result. Methods such as defining a primary hypothesis in advance or adjusting inference can address that issue, but no such strategy is reported. The registry outcome title gives Day 1 and Day 5 as time points, yet the record does not specify which contrast between those measurements and the two interventions was intended for formal inference.

Missing-data handling is also not reported. The registry does not state how missing Day 1 or Day 5 ratings would be treated, whether participants with incomplete measurements could contribute partial data, or what assumptions any method would require. It identifies the primary-outcome population as all participants who received both interventions, but does not provide the number with usable measurements or describe exclusions from the analysis.

The enrollment entry is 27, whereas safety denominators are listed as 23 for each intervention. The record does not explain the difference or establish whether it reflects participation, availability of a particular measure, or another reason. It would be inappropriate to infer an attrition pattern or analysis population from those entries alone. No interim analysis or stopping rule is reported in the registry record.

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.

Most frequent non-serious adverse event terms

The registry lists serious adverse-event entries separately for cannabis and placebo. For each group, 23 participants are listed as at risk, 0 as affected by a serious adverse event, and 0 deaths. These are the counts recorded for those categories; they do not establish that no events occurred outside the registry's defined reporting scope.

For other adverse events, the record lists 23 at risk and 13 affected in the cannabis group, and 23 at risk and 12 affected in the placebo group. The registry does not provide the terms for these non-serious events in the posted information. The serious-event terms list is empty. The entries do not describe event severity beyond the serious/non-serious categorization or provide timing, duration, or attribution.

These counts should be read as descriptive safety information, not as a complete comparative analysis. The registry record does not report statistical comparisons, uncertainty intervals, or a method for accounting for the crossover structure in the safety data. It also does not explain why the listed at-risk counts differ from the enrollment entry. Without those details, the counts do not establish whether the interventions differ in safety.

Zero recorded serious events is not equivalent to proof that an intervention has no serious risks. The registry entries describe what was reported in this record and should not be interpreted as a guarantee about outcomes beyond the study's observation and reporting.

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

The record establishes that investigators planned a randomized, quadruple-masked crossover comparison of vaporized cannabis and placebo in a study of chronic pain associated with sickle cell disease. It defines a visual analog scale pain outcome, gives its direction, and identifies Day 1 and Day 5 as measurement times. It also describes the intervention schedules and lists some adverse-event counts.

What the record does not establish is the primary pain result. It gives no mean ratings, no confidence interval for an intervention contrast, and no p-value. Therefore, it cannot show whether the observed ratings favored cannabis, favored placebo, or were similar. The stated hypotheses should not be mistaken for evidence that they were confirmed.

Nor does the record provide enough information to judge the precision of a treatment estimate. A confidence interval is named as the measure of dispersion around the mean, but the numerical interval and the method used to obtain it are absent. The number enrolled is not, by itself, the number with complete outcome data or the number included in an analysis.

The safety counts are limited descriptions of recorded events. They do not supply the types of non-serious events or a formal comparison, and they cannot demonstrate that either intervention is free of risk. Likewise, the stated objectives concerning opioid-related side effects and inflammation or disease progression do not constitute reported findings for those outcomes.

These limitations concern what can be concluded from the registry record, not necessarily every source of information about the trial. The registry status is completed, but numerical primary-outcome analyses are not posted in this record. On this record alone, the defensible conclusion is that the trial's design and intended measurements can be described, while its primary comparative pain result cannot be quantified or interpreted.

13. Why This Trial Matters Statistically

This trial is statistically notable for its crossover structure and its focus on a subjective continuous outcome. A crossover comparison can use each participant as their own reference, which may help account for stable differences between people. At the same time, the repeated measurements are related and require an analysis that respects the within-participant design. Randomization and masking describe important design features, but they do not substitute for a clear account of the analysis.

The endpoint makes the direction of the scale explicit: lower ratings mean lower pain, and higher ratings mean higher pain. That helps orient interpretation if estimates are available. Here, however, the absence of numerical pain results illustrates an important distinction between an outcome being defined and its findings being reported. Without an estimate and uncertainty interval, readers cannot assess magnitude or precision, regardless of the study's stated hypothesis.

The trial also illustrates why safety counts and efficacy outcomes should be kept distinct. The registry includes serious and other adverse-event counts, but those data do not answer the primary pain question. Conversely, the absence of posted pain estimates does not allow safety conclusions to be drawn from the endpoint definition. Each outcome requires its own results and appropriate analysis.

Finally, the record includes a completed status and a planning-illustration description, but neither is a substitute for a reported treatment-effect analysis. A planning calculation is not observed power, and administrative completion is not evidence about the direction or size of an outcome. Clear reporting of estimates, uncertainty, analysis populations, and missing-data methods is necessary for readers to judge the evidence.

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.

Several trial-specific limitations of interpretation arise from the registry information. Most importantly, numerical findings for the primary pain outcome are not reported in the registry record, despite the outcome being defined as a mean VAS score with a 95% confidence interval at Day 1 and Day 5. The record also lists zero analyses. Consequently, no estimate of the cannabis-placebo contrast or its precision can be assessed.

The record does not clarify the exact primary contrast involving the two time points. It does not say whether the intended inference concerned change over time, the Day 5 score, or another comparison. This matters because an outcome title can identify when measurements were taken without specifying the statistical question used to compare them.

Although the study is described as randomized, quadruple-masked, and crossover, important implementation and analysis details are not reported. These include the intervention sequence, washout interval, roles covered by masking, and handling of period or carryover effects. No statistical model, covariate strategy, or missing-data method is identified. The registry also does not report the number contributing to the primary endpoint.

The enrollment entry is 27, while safety entries list 23 at risk in each group. The reason for this difference is not reported, so it cannot be attributed to withdrawal, incomplete follow-up, or any other cause. The record gives counts for other adverse events but does not list their terms, and its serious-event terms list is empty. The safety data therefore have limited clinical detail.

The stated goals include opioid-related side effects and markers of inflammation and disease progression, but corresponding numerical findings are not reported in the registry record. The planning-illustration assumptions also do not constitute a reported design justification or an analysis of observed results. These gaps limit conclusions about efficacy, precision, safety, and the completeness of reporting.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Vaporized Cannabis for Chronic Pain Associated With Sickle Cell Disease — NCT01771731.
• Registry record last updated 2020-08-18; status last verified 2020-08.
• Results first posted 2020-08-18.
• 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

The registry describes a completed, randomized, quadruple-masked crossover study of vaporized cannabis and placebo for chronic pain associated with sickle cell disease. It lists Phase 1 and Phase 2, enrollment of 27, and the University of California, San Francisco as sponsor. The active and placebo interventions followed the same inhalation schedule over Day 1 through Day 5, with different listed cannabinoid contents.

The primary outcome is mean pain rating on a 0-100 visual analog scale at Day 1 and Day 5; lower scores indicate lower pain. The registry record does not report numerical primary-outcome results or analyses. Safety entries list 0 serious adverse events and 0 deaths for each group, along with other adverse events affecting 13 participants in the cannabis group and 12 in the placebo group. The record does not explain the difference between listed enrollment and safety denominators or report detailed analysis methods.