Table 4. GRADE evidence profiles for pharmacological interventions for opioid use disorder.
| Certainty assessment | Summary of Findings | Certainty | Importance | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| № of studies | Study design | Risk of bias | Inconsistency | Indirectness | Imprecision | Other considerations | ||||||
| Outcome: Mortality | ||||||||||||
| All-cause mortality in and out of MMT (Source systematic review: Sordo, 2017, 16 cohort studies) | ||||||||||||
| 16 | Observational studies | Serious a | Serious b | Not serious | Not serious | None | Pooled all-cause mortality rates were 11.3 and 36.1 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 3.20, 95% confidence interval 2.65 to 3.86) | ⨁◯◯◯ VERY LOW |
CRITICAL | |||
| Overdose mortality in and out of MMT (Source systematic review: Sordo, 2017, 11 cohort studies) | ||||||||||||
| 11 | Observational studies | Serious a | Serious c | Not serious | Not serious | None | Pooled overdose mortality rates were 2.6 and 12.7 per 1000 person years in and out of methadone treatment (unadjusted out-to-in rate ratio 4.80, 2.90 to 7.96) | ⨁◯◯◯ VERY LOW |
CRITICAL | |||
| All-cause mortality in and out of BMT (Source systematic review: Sordo, 2017, 3 cohort studies) | ||||||||||||
| 3 | Observational studies | Serious a | Not serious | Not serious | Not serious | Publication bias d | Pooled all-cause mortality rates were 4.3 and 9.5 in and out of buprenorphine treatment (unadjusted out-to-in rate ratio 2.20, 1.34 to 3.61) |
⨁◯◯◯ VERY LOW |
CRITICAL | |||
| Overdose mortality in and out of BMT (Source systematic review: Sordo, 2017, 1 cohort study) | ||||||||||||
| 1 | Observational studies | Not serious | Not serious | Not serious | Not serious | None | In the single buprenorphine cohort there were 1.4 and 4.6 fatal overdoses per 1000 person years in and out of treatment | ⨁ ⨁◯◯ LOW |
CRITICAL | |||
| All-cause mortality in LAAM maintenance vs. methadone maintenance for heroin dependence (Source systematic review: Clark et al. 2002, 11 trials) | ||||||||||||
| 11 | Randomised trials | Serious i | Not serious | Not serious | Serious j | None | Number of patients | Relative | Absolute | ⨁ ⨁◯◯ LOW |
CRITICAL | |
| LAAM | methadone | |||||||||||
| 5/760 | 1/755 | 2.28 [0.59–8.90] | 2 more per 1,000 (from 1 fewer to 10 more) | |||||||||
| Mortality in methadone maintenance treatment vs. no methadone maintenance treatment | ||||||||||||
| 4 | Randomised trials | Not serious | Not serious | Not serious | Serious j | None | Number of patients | Relative | Absolute | ⨁ ⨁ ⨁◯ MODERATE |
CRITICAL | |
| methadone | No methadone | |||||||||||
| 3/287 | 8/289 | 0.48 [0.10–2.39] | 14 fewer per 1,000 (from 25 fewer to 38 more) | |||||||||
| Outcome: Morbidity | ||||||||||||
| Hepatitis C (HCV) acquisition (Source systematic review: Platt, 2017, 12 cohort studies) | ||||||||||||
| 12 | Observational studies | Serious e | Not serious | Not serious | Not serious | Large magnitude of effect f | OST reduces the risk of HCV acquisition by 50% (risk ratio (RR) 0.50, 95% confidence interval (CI) 0.40 to 0.63, I2 = 0%, 12 studies across all regions, N = 6361), | ⨁ ⨁◯◯ LOW |
CRITICAL | |||
| Psychological Morbidity (Source systematic review: Standiford Helm 2008, 1 RCT Mattick 2003) | ||||||||||||
| 1 | Randomised trials | Not serious | Not serious | Not serious | Serious g | None | There were significant overall improvements, but no difference between groups, in psychological morbidity (GHQ and SCL90R) [No further data reported]. | ⨁◯◯◯ VERY LOW |
CRITICAL | |||
| Outcome: Substance use | ||||||||||||
| Reduction in non therapeutic opioid use (Source systematic review: Mattick 2014, 4 RCTs) | ||||||||||||
| 4 | Randomised trials | Not serious | Serious h | Not serious | Not serious | None | High-dose buprenorphine (≥ 16 mg) was more effective than placebo in suppressing illicit opioid use measured by urinalysis in the trials (3 studies, 729 participants, SMD -1.17; 95% CI -1.85 to -0.49) Notably, low-dose, (2 studies, 487 participants, SMD 0.10; 95% CI -0.80 to 1.01), and medium-dose, (2 studies, 463 participants, SMD -0.08; 95% CI -0.78 to 0.62) buprenorphine did not suppress illicit opioid use measured by urinalysis better than placebo. | ⨁ ⨁ ⨁◯ MODERATE |
CRITICAL | |||
Explanations
a. Several studies of low quality resulting from confounding bias and differential loss to follow up.
b. All-cause mortality rates varied widely across the 16 methadone cohorts (overall I2 = 98%, P<0.001), although rates were consistently higher out of treatment than in treatment
c. There was moderate heterogeneity between studies in mortality rates in treatment (I2 = 66%, P = 0.001) and strong heterogeneity in rates out of treatment (I2 = 97%, P<0.001), with significantly higher rates out of treatment among methadone patients in specialist services than in primary care
d. There was some evidence of small study effects on all-cause mortality (P = 0.05), with higher rates in small cohorts that mostly enrolled opioid injectors who were positive for HIV
e. Downgraded one level due to overall moderate risk of bias in 2 studies, overall serious risk of bias in 6 studies, 2 studies at overall critical risk of bias in 2 studies; not enough information to make judgment in 2 studies.
f. Upgraded one level due to large magnitude of the effect: RR: 0.5.
g. Imprecision downgraded due to lack of data reported. No measures reported, no effect estimates available
h. Inconsistent results related to high-, medium-, and low-dose of buprenorphine
i. The method of randomization and allocation concealment was not stated in the majority of studies, possibly due to the era in which these studies were published. It is it not known whether blinding was effective since no studies provided data to support the effectiveness of the blind
j. Too few events.