Incidence of drug injection: systematic review and meta-analysis of cohort studies among at risk populations María J Bravo Blanca I Indave EMCDDA annual expert meeting on Drug-related deaths (DRD) & Drug-related infectious diseases (DRID) 16-18 October 2013 – EMCDDA (Lisbon) Background • Initiation into drug injection is an important determinant of morbidity and mortality (blood-borne infections …HIV, HCV … and overdose). • Incidence of drug injection (IDI) is relevat Prevention/projections • IDI Cohort studies never injectors of illegal drugs/vulnerable lifestyle • Cohort studies (Coh-S) – potential of bias – Validity (internal/external) – Coh-S of hidden population presents difficultis for recruitement + high attrition lack of statistical power • There is remarkable heterogeneity between theIDI of well-known cohorts • No systematic reviews published AIMS 1. To carry out a Systematic Review of cohort studies that estimate IDI among never drug injectors at risk 2. To conduct a meta-analysis pooled IDI and explore sources of heterogeneity and bias Methods -Systematic review • Search for Cohort Studies on initiation into DI among vulnerable pop • EMBASE, Lilacs, Medline, PsycINFO. Cochrane database. 1980-2012 • MeSH, key words. No language restrictions. Published/grey literature. • Data extraction: Two independent reviewers. STROBE guidelines. • Standardize quality assessment form (SIGN50 –Scottish Intercollegiate Network-) & Drug related check list (NDARC). • Inclusion criteria: Cohort studies on initiation on drug injection: “the first documented or self-referred event of non-prescribed drug injection”. • Exclusion criteria: • No original search; Non-human study; Case report series of qualitative research • Study desing other than observational cohort (CT, C-C, C-S) • Population of former injectors at baseline • No explicit IDI, no data to compute it (new injectors/100 p-y at risk) Methods-Statistical analysis • Analysis restricted to Never-injectors at baseline that completed at least one follow-up visit • Random-effects meta-regression to: – Estimate pooled IDI and 95% CI – Identify determinants of heterogeneity – Calculate trends analysis over selected variables • Study-specific IDI were log transformed and weigheted by inverse of variance • Between study heterogeneity chi-squared test and the I2 statistic • Pooled IDI rates were calculated by: • Country (North American vs European) • % men (< 65% vs. ≥ 65%) • Mostly heroin users (no vs. yes) • Mean age(< 25 vs. ≥ 25 years) • % homeless (<50% vs ≥50%) • Mid point of follow-up period (< 2000 vs. ≥ 2000) • Recruitment methods (street-based vs • Average follow-up length (< 2 vs. ≥ 2 years). service-engaged or mixed) • Publication bias was also assessed Flow diagram of the study selection process. Potentially relevant articles identified through Data Bases PubMed: Cochrane: PsyINFO: EMBASE: Lilacs: 2794 261 862 1572 1521 Results Additional citations from Duplicated articles: 1443 rewiew of reference lists and Related Articles*: 495 • 6,063 articles identified Overall: 6063 • 13 papers selected Additional sources Excluded by Issue out of interest: provided by expert •Animals and/or molecular investigation: 456 group: 21 •Non focus on drug use: •Clinical studies: 1965 •Methodological/Economics studies : 80 Grey literature •Legal/Forensic: 65 • for cohorts originating references: 12 Others: 156 •Focus out of drugs of interest: 396 •Articles focus in diagnosis and treatment: 765 several reports we Excluded by design: selected the publication •Case series: 801 •Letter/editorial and similar: 113 with the largest baseline •Review/debate: 316 •Qualitative studies: 35 •Cross studies/prevalence studies: 317 population or the •Trial:191 •Case/Control: 317 longest follow-up period Studies of population who consumes drugs of interest that include follow-up: 121 • 9 prospective cohort studies •No data about initiation into the injection: 100 •Population who had injected drug before follow-up: were finally selected, published 55 •Population includes never injectors but results non between 1994-2012 focus on: 45 •Lack of information about time of follow-up: 3 •Lack of data about if the patients have ever injected: 3 • 1,843 participants Articles selected: 9 Characteristics of cohort studies on incidence of drug injection Results ordered by average follow-up length Men Mean Lost to Follow-up Average No. of Study, Primary drug Recruitment No. of Population age follow- follow-up new QS§ country use, baseline * (%) subjects‡ period (y) up† (%) (y) injectors Parriott, 2009, Homeless youths Cocaine Street-based 67.1 20.1 27.8 70 2004–2005 0.5 8 9 USA Valdez, 2011 Never-injecting heroin Heroin Street-based 62.6 21.4 9 219 2002–2005 1.1 43 7 , USA users Miller, 2011, Aboriginals, illicit drug Cocaine Mixed 61.9 22.2 27 197 2003–2007 1.7 39 10 Canada users ¥ Bravo, 2012, Never-injecting heroin Heroin Street-based 68.5 26 35.4 197 2001–2006 1.8 27 9 Spain users Roy, 2003, Service- HomelessStreet Youth youths Cocaine ψ 68.4 19.5 10.6 415 1995–2000 2.2 74 10 Canada engaged Mixed pattern of Service- Roy, 2011 HomelessStreet Youth youths cocaine and 72 20 17.8 352 2002–2005 2.4 37 8 engaged Canada heroine ψ van Ameijden, Methadone program Opioids (heroine or Service- 1994, The participants, drug- illegal 59 29.9 35.2 100 1985–1992 2.5 18 9 engaged Netherlands using prostitutes methadone)¶ Neaigus, Never-injecting heroin 2006 Heroin Street-based 62.7 33.2 40.5 209 1996–2003 2.6 25 10 users USA Buster, 2009 Never-injecting illicit The Cocaine Mixed 71.4 28 32.6 84 2000–2007 3.4 6 9 drug users λ Netherlands * Street-based (targeted sampling, street outreach, chain referral), service-engaged (social services, health care providers, treatment centers), or mixed recruitment; † Lost to follow-up between baseline and first follow-up visit. ‡ Participants with at least one follow-up visit; § Quality Assessment Score: Range 0 to 13.(QS); ¥ Other than marijuana; ψ A very small % might be non-illegal drug users λ Users of heroin, methadone, cocaine and/or amphetamine Study-specific IDIs and overall pooled IDI Mean Average No. of cases/ Incidence rate of initiation into drug injection Study, year age (y) follow -up (y) person-years per 100 person-years (95% CI) Parriott, 2009 20.1 0.5 8/ 33.0 24.2 ( 10.5-47.8) Valdez, 2011 21.4 1.1 43/ 232.5 18.5 ( 13.4-24.9) Miller, 2011 22.2 1.7 39/ 339.1 11.5 ( 8.2-15.7) Bravo, 2012 26.0 1.8 27/ 359.6 7.5 ( 4.9-10.9) Roy, 2003 19.5 2.2 74/ 902.4 8.2 ( 6.4-10.3) Roy, 2011 20.0 2.4 37/ 860.5 4.3 ( 3.0-5.9) van Ameijden, 1994 29.9 2.5 18/ 250.0 7.2 ( 4.3-11.4) Neaigus, 2006 33.2 2.6 25/ 543.5 4.6 ( 3.0-6.8) Buster, 2009 28.0 3.4 6/ 285.7 2.1 ( 0.8-4.6) Overall 7.8 ( 5.0-12.3) • Strong between study heterogeneity • No specific study seemed to drive the pooled IDI 1 2 5 10 20 50 The area of each square is proportional to the study weight in the meta-analysis. Horizontal lines represent exact 95% confidence intervals (CIs) based on the Poisson distribution. The diamond represents the pooled estimate from an inverse-variance weighted random-effects meta-analysis on log-transformed incidence rates. Pooled incidence rates of drug injection among never-injecting drug users by study characteristics. No. Incidence rate per 100 person- Study characteristic P value† Studies years* (95% CI) Country 0.21 North American 6 9.5 (5.5–16.2) European 3 5.2 (2.3–11.4) Mostly op/heroin users 0.82 No 5 7.4 (3.8–14.3) Yes 4 8.3 (4.0–17.0) Homeless (%) 0.44 < 50 5 6.6 (3.5–12.5) ≥ 50 4 9.6 (4.7–19.4) Recruitment 0.19 Street-based 4 10.8 (5.6–21.0) Service-eng or mixed 5 6.0 (3.3–10.9) Men (%) 0.52 < 65 4 9.2 (4.6–18.5) ≥ 65 5 6.8 (3.6–12.8) Mean age (y) 0.06 < 25 5 10.9 (6.4–18.4) ≥ 25 4 5.0 (2.7–9.3) Midpoint follow-up period 0.58 < 2000 3 6.5 (2.9–14.6) ≥ 2000 6 8.6 (4.8–15.4) Average follow-up length (y) 0.002 < 2 4 13.5 (8.5–21.3) ≥ 2 5 5.1 (3.4–7.7) • Pooled incidence rates and 95% confidence intervals (CIs) were obtained from separate random-effects meta-regression models including indicator variables for each category of the study characteristic. • † P value for heterogeneity of pooled incidence rates across categories of the study characteristic. Trend of pooled IDI by mean age at baseline 50 • 7% decrease in pooled IDI per 1-year increase Parriott, 2009 in the mean age at baseline Valdez, 2011 • pooled linear trend not significant 20 • heterogeneity remain strong Miller, 2011 10 Bravo, 2012 van Ameijden, 1994 Roy, 2003 Neaigus, 2006 per 100 person-years per 100 5 Incidence rate of initiation into drug injection drug into initiation of rate Incidence Roy, 2011 Buster, 2009 2 20 22 24 26 28 30 32 34 Mean age at baseline (y) The area of each circle is proportional to the study weight in the meta-regression. The pooled trend (solid line) and its 95% confidence band (shaded region) were obtained from an inverse-variance weighted random-effects meta-regression of log-transformed incidence rates on mean baseline ages. Trend of pooled IDI by average length of follow-up 50 • 57% decrease in pooled IDI per 1-year increase in the in the average of follow-up Valdez, 2011 • no residual heterogeneity in IDI after accounting 20 Parriott, 2009 for the follow-up length Miller, 2011 Roy, 2003 10 van Ameijden, 1994 Bravo, 2012 Neaigus, 2006 per 100 person-years 100 per 5 Incidence rate of initiation into drug injection drug into initiation of rate Incidence Roy, 2011 2 Buster, 2009 0.5 1 1.5 2 2.5 3 3.5 Average follow -up (y) The area of each circle is proportional to the study weight in the meta-regression.