Table 2.
GRADE evidence profile of medical cannabis or cannabinoids for patients with chronic pain prescribed long-term opioid therapy
| # of studies | # of Patients | FU duration (Weeks) | Risk of bias* | Inconsistency (I2, p value)† |
Indirectness‡ | Imprecision§ | Publication bias | Treatment association (95% CI) |
Overall certainty of evidence |
| Opioid dose: morphine milligram equivalents (MME) per day | |||||||||
| 4 RCTs43–45 | 1176 | 2–5 | No serious risk of bias ¶ | No serious inconsistency (40%, p=0.15) |
Very serious indirectness ** | Serious imprecision †† | Not detected | WMD −3.4 MME (−12.7 to 5.8) |
Very low |
| 8 Observational studies47 48 50 51 53–55 58 | 453 | 4–297 | Serious risk of bias ‡‡ | Serious inconsistency (visual inspection) |
No serious indirectness | No serious imprecision | Not detected | WMD −22.5 MME (−43.06 to −1.97) |
Very low |
| Pain: 10 cm VAS for pain; lower is better; the MID=1 cm | |||||||||
| 5 RCTs43–46 | 1536 | 2–5 | No serious risk of bias | No serious inconsistency (28%, p=0.20) |
No serious indirectness | No serious imprecision | Not detected | WMD −0.18 (−0.38 to 0.02) |
High |
| Sleep disturbance: 10 cm VAS for sleep disturbance; lower is better; the MID=1 cm | |||||||||
| 5 RCTs43–46 | 1536 | 2–5 | No serious risk of bias | No serious inconsistency (0%, p=0.45) |
No serious indirectness | No serious imprecision | Not detected | WMD −0.22 (−0.39 to −0.06) |
High |
| Nausea | |||||||||
| 4 RCTs43–46 | 1330 | 2–5 | Serious risk of bias | No serious inconsistency (0%, p=0.88) |
No serious indirectness | No serious imprecision | Not detected | RR 1.43 (1.04 to 1.96) |
Moderate |
| Vomiting | |||||||||
| 4 RCTs43–46 | 1330 | 2–5 | Serious risk of bias | No serious inconsistency (0%, p=0.50) |
No serious indirectness | No serious imprecision | Not detected | RR 1.5 (1.01 to 2.24) |
Moderate |
| Constipation | |||||||||
| 3 RCTs43 45 46 | 1153 | 5 | Serious risk of bias §§ | No serious inconsistency (0%, p=0.92) |
No serious indirectness | Serious imprecision †† | Not detected | RR 0.85 (0.54 to 1.35) |
Low |
*We assessed risk of bias using a modified Cochrane risk of bias instrument.
†Inconsistency refers to unexplained heterogeneity of results. For RCTs an I2 of 75%–100% indicates that heterogeneity may be considerable. We assessed heterogeneity of pooled observational studies through visual inspection of forest plots.
‡Indirectness results if the intervention, control, patients or outcomes are different from the research question under investigation.
§Serious imprecision refers to situations in which the CI includes both benefit and harm (the 95% CI includes 1 MID).
¶Some of the included RCTs were at high risk of bias, due to loss to follow-up (>20%); however, we did not rate down for risk of bias as subgroup analysis showed no difference in treatment effect between trials at high and low risk of bias for missing outcome data (test of interaction p=0.758 and p=0.623 for opioid dose reduction and pain respectively).
**Downgraded twice due to indirectness since all trials instructed participants to maintain their opioid dose during the study period.
††The 95% CI around the WMD includes no effect.
‡‡Studies are based on non-representative samples.
§§Most RCTs were at high risk of bias due to lost to follow-up (>20%).
FU, follow-up; GRADE, Grading of Recommendations Assessment, Development and Evaluation; MID, minimally important difference; RCT, randomised controlled trial; RR, relative risk; VAS, Visual Analogue Scale; WMD, weighted mean difference.