Additional data available from criminal justice sources provided evidence of duplicated identifiers for 23% of cases (n = 58,547 of 256,794); conservatively, all records for these were excluded from the current analysis. Case-linkage to mortality records used the additional criterion of region of residence, to increase accuracy. Linked mortality records (n = 478) were removed where evidence of new treatment

or criminal justice activity, after the apparent date of death, indicated an erroneous match. Data were rendered anonymous to the research team, via irreversible encryption of identifying information, prior to their release by source organisations. The Office for National Statistics provided records of deaths of persons aged 18–64 years occurring

during the observation period 1st April, 2005 to 31st Icotinib in vitro March, 2009 and registered by 30th September, 2011. This allowed for late registration of deaths referred for investigation by a coroner (Bird, 2013). Underlying cause was recorded for each death and coded according to the World Health Organisation’s International Classification of Disease 10th revision (ICD-10; WHO, 2011). Population mortality rates were compiled from mid-year population estimates and published figures on deaths registered between 2005 and 2008 for England and Wales (Office for National Statistics Statistical Bulletin, 2011) as published data were not available by death-year for the exact observation period. Rates were calculated by gender, five year age-group (15–19, 20–24, 25–29, 30–34, 35–39, 40–44, 45–49, 50–54, 55–59, 60–64), and for underlying cause of death. Drug-related poisoning deaths were defined according LY2835219 chemical structure to the Office of National Statistics UK harmonised definition (Office for National Statistics Statistical Bulletin, 2013) which uses the following ICD-10 codes: F11-16, F18-19 (mental and behavioural disorders due to psychoactive substance use, excluding alcohol and tobacco); X40-44 (external causes: accidental poisoning by drugs, medicaments and biological substances); X60-64 (external causes: intentional self-poisoning drugs, medicaments and biological substances);

X85 (external causes: assault by drugs, medicaments and biological substances); Y10-14 (external causes: Megestrol Acetate poisoning by drugs, medicaments and biological substances undetermined intent). Suicides include deaths of ‘undetermined intent’ (ICD-10: X60-X84; Y10-Y34). To avoid double counting, drug-related poisoning mortality was treated as a separate category and were excluded from reporting of the ICD-10 Chapters ‘external causes’ and ‘mental and behavioural disorders’. Use of official mortality records was approved by the Office for National Statistics Microdata Release Panel. Use of data from the Drug Data Warehouse was authorised by those organisations providing data. The NHS Central Office for Research Ethics Committees and The University of Manchester Research Ethics Committee advised that further approval was not required for a study of this type.