1. QResearch - latest research Professor Julia Hippisley-Cox September 2015 EMIS National User Conference

2. + Co-authors QResearch database EMIS & Contributing EMIS practices EMIS National User Group University of Nottingham QResearch Advisory Board ClinRisk (software) Co-authors QResearch database EMIS & Contributing EMIS practices EMIS National User Group University of Nottingham QResearch Advisory Board ClinRisk (software) Acknowledgements

3. QResearch Databases – Governance – Coverage Examples of studies – QDiabetes -risk of complications – Hypoglycaemic drugs – VTE & oral contraceptive Questions Overview

4. Set up in 2002 by EMIS and University of Nottingham Support from EMIS, RCGP, BMA, SAPC REC > 1000 practices EMIS Web > 20 million patients (current and historical) Coded longitudinal data for 20+ years – Socio-demographics – Diagnoses – Clinical values & tests – Prescription data – Consultation data No patient identifiers – pseudonymised-at-source Now linked to HES, ONS, Cancer register QResearch

5. Provides oversight for QResearch Principles and policy for access to data Oversees communication with & benefits back to patients & practices Includes professional & patient representation – EMIS & EMIS NUG – Patient advisers – RCGP & SAPC – BMA – UoN QResearch Advisory Board

6. Only used for research projects Testing or generating hypotheses Must have research question & protocol Must pass scientific review Lead researcher based in UK university Data only used for stated purpose No onward sharing of data Results must be published What can QResearch used for?

7. Advisory Board Membership, ToR & minutes Patient Information Practice Information Researcher Information List of all papers & reports using QResearch data Description of ongoing studies Power point presentations Information on QResearch website

8. Open to any EMIS Web or PCS in Scotland Read information sheet on qresearch.org Display patient information in waiting room, website Activate data sharing agreement https://www.emisnug.org.uk/enabling-sharing- agreements-qsurveillance-and-qresearch https://www.emisnug.org.uk/enabling-sharing- agreements-qsurveillance-and-qresearch Contributing to QResearch

9. Already in EMIS Web QRISK2 QDiabetes QStroke QFracture QAdmissions QCancer In planning phases QKidney QThrombosis QBleed QScores and EMIS Web

10. Risk of Complications in Patients with Diabetes

11. Risk of diabetes complications Diabetes associated with micro & macrovascular complications Intensive control risk factors lowers incidence microvascular complications. Most patients little idea of risk – over-estimate risk of complications – over-estimate benefits of treatment Amputation & blindness most feared & most affect quality of life Ba Background

12. Aims To quantify risk of complications in people with type 1 or type 2 diabetes – Amputation – Blindness – Heart failure – Kidney failure (www.qkidney.org)www.qkidney.org – Cardiovascular disease (www.qrisk.org)www.qrisk.org Better information for patients to inform decisions Better tools to risk stratify patients to match interventions to level of risk Aims

13. Methods Cohort study people with type 1 & type2 diabetes Follow up over 15 years Measure risk factors at baseline Measure outcomes (amputation/blindness/CCF) Develop risk prediction algorithms ‘Validate’ tools to make sure it works well CCF results published BMJ open Amputation/blindness in press BMJ Methods

14. www.qcancer.org Chronic kidney disease Atrial fibrillation Heart failure Peripheral vascular disease Rheumatoid arthritis Blood pressure treatment Age Sex Ethnic group Deprivation Smoking status Type of diabetes Duration of diabetes HBA1C Cholesterol/HDL Systolic blood pressure Clinical values Comorbidity Demography/ lifestyle Key Factors in Model

15. www.qcancer.org Web calculator www.qdiabetes.org/complications 70 yr old man Ex-smoker Type 2 for 3 years HBA1C 100 SBP 150 10 year risk CVD = 35% CCF= 13% < 5% risk amputation < 5% risk blindness

16. www.qcancer.org Limited trial evidence of effectiveness of hypoglycaemic drugs on outcomes Most focus on surrogate measures HBA1C Using QResearch linked data to look at key outcomes Heart disease Kidney disease Blindness Amputation Cancer New study on risks/benefits hypoglycaemics Gliptins Insulin Other agents Sulphonyl ureas Metformin Glitazone

17. Risk of Thrombosis in Women taking the Oral Contraceptive Vinogradova, Y Coupland C, Hippisley-Cox J. BMJ 2015

18. Introduction  Exposure 9% worldwide, 18% developed countries, 28% UK  Effective for preventing pregnancy  Earlier COC Norethisterone (1960s) Levonorgestrel (1970s)  Newer COC Norgestimate (1980s) Desogestrel (1980s) Gestodene (1980s) Drospirenone (2000s )  Aim: Examine risk of VTE for most common types of the Pill taking account of other patient characteristics COC – combined oral contraceptives Risk of VTE and Oral Contraceptive

19. Methods: Study design Nested case control study Study period Jan 2001– Dec 2013 Aged 15 – 49 At least 1 year of records Up to 5 controls matched by –Age, practice –Calendar year Exclusions: –previous VTE/ AC therapy, sterilisation, pregnancy Methods: study population

20. Methods: Exposure to the Pill Terms of use Current use (within 28 days ) Short term (up to 84 days) Long term (more than 84 days) Exposure to only one current COC Past use (29 to 365 days) Types of progestogen Norethisterone Levonorgestrel Norgestimate Desogestrel Gestodene Drospirenone Cyproterone Other contraceptives Progestogen only pill Non-oral contraceptives Dose of oestrogen 20µg 30µg or more Methods: exposure to COP

21. Methods: Confounders Chronic conditions (cancer, congestive cardiac failure, varicose veins, congestive cardiac disease, rheumatoid arthritis, Systemic lupus erythematosus, renal disease, asthma, Chronic obstructive pulmonary disease, Crohn’s disease or colitis, coagulation disturbances) Immobilisation (last 6 months) (acute infection, surgery, hospitalisation, fracture) Body mass index, smoking, alcohol, ethnicity Polycystic ovary syndrome Methods: things we can take into account

22. QRESEARCH Progestogen %cases %controls Any COC 28.416.3 Norethisteron2.71.7 Levonorgestrel12.68.5 Norgestimate3.52.1 Desogestrel3.71.6 Gestodene2.61.1 Drospirenone2.31.1 Cyproterone2.81.2 CPRD Results: Use in the last year Progestogen %cases %controls Any COC 29.518.3 Norethisteron2.71.7 Levonorgestrel13.49.9 Norgestimate3.22.5 Desogestrel3.91.5 Gestodene1.91.0 Drospirenone3.31.4 Cyproterone3.41.4 5,500 cases 5,062 cases Use of different types Progestogen

23. Fig 3 Adjusted odds ratio for VTE in patients currently exposed to combined oral contraceptives compared with no use in the last year, by database. Yana Vinogradova et al. BMJ 2015;350:bmj.h2135 ©2015 by British Medical Journal Publishing Group

24. Numbers needed to harm Progestogen typeNumbers needed to harm over 1 year Extra cases per 10 000 treated per year Norethisterone 15297 Levonorgestrel 17396 Norgestimate 15616 Desogestrel 72914 Gestodene 90511 Drospirenone 76613 Cyproterone 73114 Note risk still lower than VTE risk during pregnancy Numbers needed to harm

25. Conclusions The largest study providing reliable comparable findings with earlier large-scale studies Completely independent of pharma Based on British population and prescribing practice Able to drill down to level of individual drug Newer drugs higher risks than older drugs Drugs containing gestodene, desogestrel, drospirenone & cyproterone higher risks than levonorgestrol or norgestimate Conclusions

26. Drug-safety projects Risk of GI bleeding in patients taking Cox-2 inhibitors or NSAIDS Risk of myocardial infarction in patients taking Cox-2 inhibitors or NSAIDS. The effect of statins on mortality in patients with ischaemic heart disease Risk of pneumonia in patients taking statins: Unintended effects of statins in men and women Exposure to Cox-2 and NSAIDs and risk of Cancer Risk of colorectal cancer in patients taking statins and NSAIDs Exposure to Statins and risk of common cancers Risk of cancer in patients with diabetes prescribed glitazones Risk of cancer with bisphosphonates Antidepressant use and the risk of adverse outcomes in older people Safety of smoking cessation treatments Antipsychotic medication and risk of thromboembolism Risk of bleeding in patients prescribed NOACs (novel anticoagulants) Other Drug Safety Studies

27. Any questions