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Ninewells Hospital & Medical School
Research and Trials within BIHS
Tom MacDonald
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Salty tablets increase hypertension seven-fold and double mortality
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UK Research Paper of the year Nomination
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Our Consortium
•University of Dundee (lead)•University of Strathclyde•University of Glasgow•University College London•University of Southern Denmark• ISD Scotland
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The need for randomisation in the study of
intended effectsMiettinen OS
Stat Med 1983;2:267-71
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Practice does not usually change as a result of observational studies
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Lancet 2015
Lancet Editorial 2015
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Lancet 2015;386:2059–68
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Shortlisted again (one of 5)
Did not win (again)
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SCOT Study• >9400 patients screened
• >7300 patients randomised
• Mean FU ~ 3.2 years
• 706 GP practices
• 10 centres
• 3 EU countries
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Lee S SimonHarvard then FDA
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Prescribing
Hospital Diagnoses
Death Certification
Lab data
Joined-up NHS
NHS: Randomise within a database
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Gertrude Elion George HitchingsJames Black
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MEMO
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Allopurinol and cardiovascular outcomes in patients with ischaemic
heart disease (ALL-HEART)
Funded by the National Institute for Health Research, Health Technology Assessment Programme (www.nihr.ac.uk)
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ALL-HEART summary• Does allopurinol improve cardiovascular
outcomes in patients with IHD?• Funded by UK NIHR HTA • Target 5,215 patients with IHD
• Randomised to:Allopurinol 600mg or 300mg added to usual care
vsUsual care
• PROBE Design• Followed up for average of 4 years
– Electronic record-linkage– Annual questionnaire sent by research team– Study ends when 631 events have occurred
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22
ALL-HEART GP Sites
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MEMO
EMA Regulatory Commitment
Post licensing safety study
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Why do ‘Industry Research’
• Industry studies: generate infrastructure
=
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BMJ 2008;337:1085-7
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TIME Subjects
19,191
1,887
6
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MEMO
Time Study Song on YouTube
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Randomising Patients
• Poor external validity– Only those interested in health participate
– Low event rates
• Expensive
• Bureaucratic
• Time consuming
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Evidence Study
BFZ
New Policy
Old Policy
Participating Practices
Indapamide
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Advantages of Cluster Randomised Rx policy
• Good external validity
• Efficient
•Quicker
• Cheaper
•Opt-out, not opt-in.
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Clinical Trials Unit
Not CTIMP Study
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All trials fully recruited>32,000 patients Randomised
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ProblemInvite 100 suitable
subjects
Randomise 10-14 (healthy people)
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Mr Average
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Few Deprived
Few Very Old
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Estimated CV event rate> 2.5% / year
Observed adjudicated CV event rate
< 0.9% / year
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People interested in their health
Have a low CV event rate
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The Drug Song• There's Aspirin, Adrenaline & also Aminophylline,
• Amphetamine, Adenosine, Aldactone & Rifampicin,
• Gentamicin, Bromocriptine, Heparin & Warfarin
• All drugs that are quite hard to use but also relieve suffering
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Verse 2• There's Hydrochlorothiazide & also Cyclophosphamide
• & Metoclopramide, Acetazolomide Tropicamide,
• Loperamide, Amiloride & Cyclizine & Frusemide
• and if you think you’re pregnant then you best avoid Thalidomide.
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Verse 3• There's Lithium, Fluoxetine & also Amitriptyline,
• Paroxetine, Digoxin, GTN & Azathioprine,
• Miconazole, Atenolol & also Chloramphenicol
• & if you want to overdose there's always Paracetamol.
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Verse 4• There's Nabumetone & Phenytoin, Zirtek & Diazepam,
• & Lithium, Temazepam, Midazolam, Clonazepam,
• Testosterone, Aldosterone & Valium & Insulin,
• & those of us with ADH still need to take our Ritalin
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Verse 5• There's Cefuroxime, Cefotaxime, Cefalexin, Cephedrine,
• & Chloramphenicol & Ketoconazole, Trimethoprim,
• Erythromycin, Macrolides, and other tablets every day
• that taken lots are bound to cause Clostridium difficile
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Verse 6• There's Alcohol & Nicotine, for which you’ll need a PPI
• & Cannabis & Heroin, from which you hope you get a high
• There’s Ecstacy & Methadone & Speed and even raw Cocaine,
• All drugs that make you want to take them all again and then again
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Verse 7• Ritixumab, imatinib, mycophenalate mofetil
• Levetiracetam, abciximab are drugs that I can’t spell
• We give them simple names like MabThera, Glivec and ReoPro
• And put these on the pens so the proprietary names we know
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Final Bit• Now:• You must remember all these drugs
• The names that you have learned from me
•Or sod it all & get a job in Orthopaedic Surgery