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Ninewells Hospital & Medical School Research and Trials within BIHS Tom MacDonald
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The FAST Study Febuxostat vs Allopurinol Streamlined Trial ...

Oct 31, 2021

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Page 1: The FAST Study Febuxostat vs Allopurinol Streamlined Trial ...

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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Febuxostat versus Allopurinol Streamlined Trial

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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