Sativex and Behavioral-relapse Prevention Strategy in Cannabis Dependence: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Sativex and Behavioral-relapse Prevention Strategy in Cannabis Dependence (NCT01747850), a randomized phase 2 study. The primary outcome is Tolerability.

2. Clinical Question

The central comparison concerns the count of participants who withdrew due to serious adverse events, not the count of all serious adverse events or all reasons for withdrawal. The registry reports zero such withdrawals in the Sativex group, zero in the placebo group, and zero in the pilot group. These observed counts describe the participants represented in the registry results; they do not establish that the underlying risk is absent.

The study also posted secondary measures of cannabis use in days, cannabis use in grams, and craving at six months. Those measures address different aspects of the treatment question and should not be treated as substitutes for the primary tolerability outcome. Because the pilot was open label and did not have a placebo control, its observations do not provide a randomized comparison with the placebo group.

3. Trial Design

The registry identifies this as a phase 2, randomized, parallel-group trial with triple masking. The planned treatment comparison was Sativex spray versus placebo spray, with both groups receiving a weekly intervention combining Motivational Enhancement Therapy and Cognitive Behavioral Therapy. The registry record’s brief description characterizes the main medication study as a twelve-week, double-blind, placebo-controlled study; its design fields separately specify triple masking. The record does not explain this difference in wording.

An initial pilot component involved five treatment-seeking subjects receiving Sativex open label, without a placebo control. The brief description says the pilot was intended to assess whether the planned self-titration regimen was appropriate. It then describes a placebo-controlled medication phase with a planned n=40. The registry lists enrollment as 45. These descriptions distinguish the pilot from the randomized comparison, but the record does not provide a participant flow accounting for enrollment, completion, and analysis.

The behavioral intervention was delivered weekly. The brief description also says participants were expected to attend the centre daily to assess medication use, followed by weekly follow-up for another four weeks and then monthly follow-up until the six-month visit after the target quit date. These are descriptions of the planned study schedule; the registry does not report adherence to each visit or the completeness of follow-up.

The study is recorded as completed, with a start date of 2013-03 and primary completion in 2015-11. The sponsor is the Centre for Addiction and Mental Health. The record does not report a detailed statistical analysis plan, allocation concealment procedures, or the method used to preserve masking.

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 Tolerability, measured over six months.

The primary endpoint is tolerability, operationalized as the number of participants who withdrew from the study because of serious adverse events during the six-month timeframe. In the registry results, the count is zero for Sativex, zero for placebo, and zero for the open-label pilot. This endpoint concerns a specific consequence of serious adverse events: withdrawal attributed to them. It is not a count of every adverse event, a measure of symptom severity, or a complete account of treatment discontinuation for other reasons.

As a general statistical rationale, withdrawal due to a serious adverse event can be a clinically relevant tolerability measure because it captures an event consequential enough to lead a participant to leave the study. Using a clearly defined count also makes the endpoint straightforward to describe. However, a count alone does not characterize the nature, timing, duration, or severity of events, and it does not capture events that did not lead to withdrawal.

The endpoint is therefore narrow. Its interpretation depends on consistent definitions and ascertainment of serious adverse events, and on accurate attribution of withdrawal reasons. The registry does not report further details about those procedures. Zero recorded withdrawals in each group means that none were reported for this endpoint in the posted results; it does not show that no serious adverse events occurred. The separate adverse-event results report zero participants with serious adverse events in the listed groups, while reporting other adverse events separately.

7. Results Posted in the Registry

• Sativex # of Participants That Withdrew Due SAE: 0.0% (0/20) versus 0.0% (0/20) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Cannabis Use (in Days)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Sativex % Days Use of Cannabis: mean 42.90 versus 47.10 on control; difference -4.20 (95% CI -10.78 to 2.38), standardized effect d = -0.40; z-test p = 0.211.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sativex % Days Use of Cannabis and the control. The interval gives the range of effects that remain compatible with the data.

Cannabis Craving

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • Sativex Craving: mean 8.20 versus 9.60 on control; difference -1.40 (95% CI -4.53 to 1.73), standardized effect d = -0.28; z-test p = 0.381.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sativex Craving and the control. The interval gives the range of effects that remain compatible with the data.

Cannabis Use (Grams)

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard errors.
• Result:
  • Sativex Cannabis Use (g): mean 2.30 versus 3.50 on control; difference -1.20 (95% CI -4.08 to 1.68), standardized effect d = -0.26; z-test p = 0.415.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Sativex Cannabis Use (g) and the control. The interval gives the range of effects that remain compatible with the data.

Across the posted secondary outcomes, the Sativex group’s point estimates are lower than the placebo group’s, while the comparison intervals include no mean difference. This is a consistent direction in the summaries, but the uncertainty means that the apparent pattern should not be treated as a demonstrated treatment effect. The outcomes represent different aspects of cannabis use and craving, so agreement in direction is worth noting without treating them as interchangeable measures.

These secondary results complement the primary tolerability result but answer a separate question. The primary endpoint concerns withdrawals caused by serious adverse events. The secondary endpoints concern average reported cannabis use and craving at six months. Similarity or difference in one type of outcome does not determine the result for another. Nor does a tolerability count establish an effect on cannabis use or craving.

The unadjusted secondary comparisons carry less weight than a prespecified primary analysis would because the registry does not report a testing hierarchy, multiplicity adjustment, or reported analyses for them. As a general statistical issue, interpreting many outcomes independently increases the risk that a seemingly notable result occurs by chance. The record does not state whether the secondary outcomes were planned as confirmatory, and the posted p-values should not be used as isolated proof of benefit or lack of effect.

These outcomes also depend on measurement and follow-up. The registry gives six-month summaries but does not report how missing observations were handled, whether results reflect all randomized participants, or how cannabis use and craving were assessed in the final analysis. Without those details, the summaries are best viewed as exploratory descriptions of the available results, not as a complete account of longitudinal treatment response.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Cannabis Use (in Days)
• Withdrawal
• Cannabis Craving
• Cannabis Use (Grams)

9. Statistical Interpretation

10. Statistical Methods Explained

Statistical methods help distinguish what an observed result says from what remains uncertain. The registry reports counts for the primary tolerability endpoint and means with measures of spread for the continuous secondary outcomes. The comparison figures for secondary endpoints are unadjusted summaries calculated from the posted group statistics; the record lists no reported analyses for them. The statistical analysis plan, including any adjusted models or prespecified testing sequence, is not reported in the registry record.

What does a risk difference describe?

As a general explanation, a risk difference compares the proportion with an event in one group with the proportion in another group. A value of 0.0 indicates that the observed proportions are the same. For this trial, the event is withdrawal due to a serious adverse event. No such withdrawals were recorded in either randomized group, so the posted difference is 0.0. This comparison is specific to that defined event and does not compare every possible safety outcome.

A difference calculated from observed group counts is not a guarantee about the difference that would be seen in a larger population. Statistical uncertainty generally matters especially when events are uncommon or absent. The reported interval for the primary comparison also has both bounds at 0.0. The registry does not describe the method used to construct that interval, so its form should not be taken as evidence that uncertainty about the underlying event risk has disappeared.

How should mean differences be read?

For continuous outcomes, a mean difference expresses the difference between group averages in the original measurement units. A negative value in these comparisons indicates a lower average in the Sativex group than in the placebo group, given the order used in the comparison. The posted estimates are unadjusted, meaning they are not presented as results from a model accounting for other participant characteristics or design features. The registry does not report adjusted analyses.

The secondary outcome summaries also include standard deviations for cannabis use in days and craving, and standard errors for cannabis use in grams. As a general explanation, a standard deviation describes variability among individual observations around a group mean. A standard error describes uncertainty in an estimated mean. They are not interchangeable, so the spread measure should be interpreted according to the particular outcome’s stated definition. The record does not give participant-level data that would permit additional checks of distributions or assumptions.

What does an unadjusted p-value contribute?

As a general explanation, a p-value describes how compatible observed data are with a specified null hypothesis under the assumptions of the analysis. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The secondary p-values are explicitly unadjusted. The record does not state that they were part of a confirmatory testing plan, and it lists no reported analyses. They should therefore be read alongside the estimated differences and intervals, rather than as standalone decisions.

When several outcomes are examined, the chance of at least one apparently unusual result can increase. As a general statistical issue, multiplicity procedures can control error rates across a prespecified family of tests, but the registry does not report whether any such procedure was planned or used. It also does not report which secondary endpoint, if any, was intended to be confirmatory.

What do the planning illustrations mean?

The sample-size illustrations use the observed secondary-outcome effects as a basis for planning calculations. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, a normal approximation, and effects set at the stated fractions of the observed effects. These calculations are planning illustrations, not observed power and not the trial’s own design justification. The registry record does not report the original sample-size assumptions or justification. The illustrations do not establish that a future study should use those effects, nor do they guarantee that a future study will achieve its target power.

As a general explanation, over-dispersion matters when the variability in data is greater than a model’s assumptions allow, because standard errors and uncertainty estimates may then be too small. The posted continuous summaries do not provide enough detail to assess distributional shape or model fit. No count-data model, over-dispersion assessment, interim analysis, or missing-data method is reported in the registry record.

11. Confidence Intervals and Precision

A confidence interval describes a range of estimates compatible with the data under the method used to construct it. As a general explanation, a wider interval indicates less precision, while an interval that includes no difference means the data do not clearly distinguish a nonzero difference from no difference at the stated confidence level. The registry does not state the confidence level or construction method for the intervals displayed with the secondary comparisons.

For the primary comparison, the reported risk difference is 0.0 and its bounds are 0.0 to 0.0. This conveys no observed difference in the recorded withdrawal counts. It should not be interpreted as proof that the underlying risks are exactly equal. With zero events in both randomized groups, the observed data cannot reveal how the groups would compare for an uncommon event in a broader population. The registry does not report the interval method, so the stated bounds cannot by themselves support a broader claim about precision.

The secondary comparison intervals extend across both negative and positive values for each outcome. In practical terms, the posted summaries are compatible with differences in either direction as well as with no difference. The point estimates alone do not resolve that uncertainty. Their precision is also limited by the group sizes and the variability reported in the outcomes; the registry does not provide participant-level distributions or adjusted estimates that could refine interpretation.

The planning illustrations are not a substitute for uncertainty intervals around observed effects. They show participant requirements under stated assumptions for detecting selected fractions of the observed effects at stated power targets. Because those effects come from this study’s estimates, they may be unstable; the illustrations are not observed power and are not the registry’s original sample-size justification.

12. Multiplicity, Missing Data and Analysis Populations

The registry record does not report a statistical analysis plan, a hierarchy of endpoints, or a method for adjusting secondary tests for multiplicity. It lists one primary endpoint and multiple secondary outcomes, but does not explain whether the secondary outcomes were confirmatory, exploratory, or selected for posting after analysis. This matters because the interpretation of individual p-values depends partly on how many hypotheses were considered and how those tests were intended to be used.

As a general explanation, testing multiple outcomes can increase the chance of at least one result appearing unusual by chance. A prespecified adjustment or testing sequence can address that issue, but no such approach is reported in the registry record. The secondary p-values are therefore unadjusted summaries and should not be treated as a family of confirmatory findings. The record also does not report interim analyses or stopping rules.

Missing-data procedures and analysis populations are not reported in the registry record. There is no description of how participants with incomplete follow-up were handled, whether imputation was used, or whether analyses followed an intention-to-treat or per-protocol principle. The outcome summaries report group counts, but those counts alone do not establish which participants were included in every analysis or whether missing observations affected the estimates.

The record does not provide a participant flow diagram or detailed accounting of withdrawals, exclusions, and outcome availability. This is particularly relevant because withdrawal due to serious adverse events is the primary endpoint, while other reasons for discontinuation may affect the completeness of secondary follow-up. Without these details, the posted results cannot establish how missingness may have influenced estimates. These are reporting limitations; they do not show that a particular analysis method was or was not used.

13. Safety Results

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

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent non-serious adverse event terms

The primary safety-related result counts withdrawals attributed to serious adverse events. The registry reports zero such withdrawals in the Sativex group, zero in the placebo group, and zero in the pilot. This is a finding about withdrawal for that specified reason, not proof that no serious adverse events occurred. The adverse-event listing separately reports zero participants affected by serious adverse events in each group, and no serious adverse event terms are listed.

Other adverse events are reported for 16 participants in the Sativex group, 18 in the placebo group, and four in the pilot group. These are separate from the serious adverse event counts and from the primary withdrawal endpoint. The registry does not provide event descriptions or severity breakdowns for these other events in the available record. Deaths are not reported in the registry record.

Small groups and zero recorded serious events limit the strength of conclusions about uncommon harms. The open-label pilot is also distinct from the randomized comparison and should not be pooled with it as though it were a randomized arm. These results describe the posted counts; they are not a complete safety profile or advice about treatment.

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

The posted primary result supports a narrow statement: no participant in any listed group was recorded as withdrawing because of a serious adverse event. The randomized comparison’s estimated difference for this endpoint is 0.0. This describes what was observed in the registry results, not the exact underlying risk in all people with cannabis dependence or in future use of the treatments.

The result does not establish that Sativex and placebo have identical safety profiles. A study with no observed primary events cannot reliably distinguish between possible underlying risks for an uncommon outcome. It also does not imply that no adverse events occurred: the registry reports other adverse events in each group. Nor does the primary endpoint measure every reason for stopping treatment or every dimension of tolerability.

The secondary summaries do not turn the primary result into evidence of efficacy. They describe average cannabis use and craving at six months, with uncertain comparisons. Their directions and intervals require cautious interpretation because the analyses are unadjusted and the registry does not report multiplicity handling, missing-data methods, or participant-level analyses. The available summaries do not justify a broad conclusion about whether treatment changes cannabis use or craving.

The trial design includes a randomized placebo-controlled component, which is useful for comparative interpretation, and a separate open-label pilot that does not offer the same controlled comparison. The registry’s description of masking is not fully aligned across its design fields and brief description, and it does not explain the difference. Overall, the posted data are best read as limited descriptive evidence about the recorded groups and outcomes, not as a definitive answer about safety or treatment effects.

15. Why This Trial Matters Statistically

Statistically, this study illustrates how an endpoint can be clearly defined yet remain difficult to estimate when the event is rare. Counting withdrawals due to serious adverse events is straightforward to describe, but zero recorded events in the randomized groups do not establish that the underlying risks are equal or absent. The distinction between an observed count and an estimate of population risk is central to interpreting safety results.

The design also contains different kinds of evidence. A randomized comparison of Sativex and placebo is structurally distinct from the open-label pilot. Keeping those components separate avoids treating pilot observations as if they arose from a controlled allocation. The behavioral intervention was part of both randomized treatment strategies, so the posted comparison concerns medication assignment alongside that shared intervention, not medication in isolation from behavioral care.

The secondary outcomes show another important issue: several related endpoints may produce a broadly consistent direction while still leaving substantial uncertainty. Unadjusted tests do not account for the number of outcomes considered, and the registry does not report a prespecified testing strategy. Intervals, analysis plans, and missing-data procedures are therefore important to interpreting results beyond the displayed averages.

Finally, planning calculations based on observed effects are not evidence that the original study was adequately powered, nor are they a replacement for a protocol-based design rationale. The registry does not report that rationale. The record is a useful example of why statistical interpretation should separate primary from secondary outcomes, randomized from pilot evidence, observed data from planning assumptions, and absence of observed events from evidence of no risk.

16. 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 limitations specific to this record constrain interpretation. The primary endpoint is limited to withdrawal due to serious adverse events, while the registry does not give detailed descriptions, timing, or attribution procedures for adverse events. It also does not report deaths. The other adverse event counts are not accompanied by a detailed event listing in the available record, limiting assessment of the types or severity of events.

The pilot was open label and had no placebo control, so its outcomes cannot be interpreted as a randomized treatment comparison. The registry’s brief description calls the main study double blind, while the design field specifies triple masking; the record does not clarify the difference. It also does not report allocation concealment or the practical methods used to maintain masking.

For the six-month secondary outcomes, the record provides group summaries and unadjusted comparisons but no reported analyses, participant-level distributions, adjusted estimates, or missing-data methods. It does not identify the analysis population or show a detailed flow of participants through follow-up. The absence of these details makes it difficult to judge whether incomplete observations or analytic choices affected the reported summaries.

The record does not report the trial’s statistical analysis plan, multiplicity strategy, interim analyses, stopping rules, or sample-size justification. Planning illustrations based on observed effects cannot fill those gaps. These limitations concern what can be established from the registry record; they do not determine what methods investigators may have used outside the reported information.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Sativex and Behavioral-relapse Prevention Strategy in Cannabis Dependence — NCT01747850.
• Registry record last updated 2017-10-02; status last verified 2017-07.
• Results first posted 2017-10-02.
• 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.

20. Record Summary

The registry describes a completed, randomized phase 2 parallel-group study of Sativex spray versus placebo spray alongside weekly Motivational Enhancement Therapy and Cognitive Behavioral Therapy. It also includes a separate open-label Sativex pilot. The primary endpoint is the number of participants withdrawing due to serious adverse events over six months.

No such withdrawals are reported in the Sativex, placebo, or pilot groups. The record also posts six-month secondary outcomes for cannabis use and craving, with unadjusted comparisons and no reported analyses. Statistical analysis details, missing-data methods, and multiplicity procedures are not reported in the registry record.