Rationale and Practicalities of Drug Testing Lynn Hillyer Lynn Hillyer, BVSc, PhD, MRCVS, Veterinary Adviser, BHA

1. Rationale and Practicalities of Drug Testing Lynn Hillyer Lynn Hillyer, BVSc, PhD, MRCVS, Veterinary Adviser, BHA as part of the ‘Medicating/Treating the Competition Horse’ session BEVA Congress, Liverpool, September 2011

2. Why drug test? What is the rationale? • The horses we are talking about are competitors • Sport should be fair ‘in sport, the spirit of fair play prevails’ (Olympic Charter) • Sport should be safe for its competitors, here of course the horses, ‘encourage and support measures protecting the health of athletes’ • Racing: IFHA Article 6 sets out an internationally agreed position, horses must race free from the effects of drugs for their welfare, their jockey’s safety and the integrity of the sport

3. Vets & medication regulation • Medication is part of equine veterinary practice • Equine vets have a professional duty – RCVS Oath, ‘promise above all that ..my constant endeavour will be to ensure the welfare of the animals committed to my care’ • In sport, there is a significant public aspect – confidence in the profession; AWA 2006 • BHA/other international racing/horse sport regulators do not regulate vets but the Rules affect vets via their clients and inappropriate behaviour in that context will inexorably lead to other regulators stepping in - RCVS, VMD... • Although the vast majority work within the Rules, there have been recent cases in which veterinary surgeons looking after racehorses have not lived up to this Oath, behaved professionally or kept within the law

4. What are equine vets/trainers doing? Two different ways of looking at things • ‘We’ll prescribe all the medications we can – both pre-emptively and as close to competition as we can because that’s ‘in the best welfare interests of the horse (that’s what my client demands, it’s the ‘edge’ I market and I don’t want to lose him/her)’ with the aim at all times that they are not detected/I’ll get away with what I can Or .. • ‘We’ll use medication judiciously, acting as veterinary surgeons, to diagnose then treat clinical conditions, advising that those horses that cannot train/compete should have (relative) rest. When a client demands otherwise we have the integrity to tell them to go to another vet’ • Racing: although the reality may be option 1, trainers must comply with the latter under Rules

5. What do trainers have to do? • 27. Duty to promote welfare of horses 27. A Trainer must take all reasonable steps to ensure the safety and welfare of all horses under his care or control (whether or not they are currently in training). • 28. Veterinary treatment and medication 28.1 A Trainer must ensure that all treatments and medication administered to a horse under his care or control are given in the interests of its best health and welfare. 28.2 Accordingly 28.2.1 every treatment must be fully justifiable by the medical condition of the horse receiving the treatment,28.2.2 horses that are not trainable as a result of injury or disease must be given appropriate veterinary treatment before training is resumed, and28.2.3 the Trainer must obtain advice from the Veterinary Surgeon prescribing a treatment as to the appropriate level of training during the duration of the treatment.

6. 13. Duty to keep medication records 13.1 A record of any Treatment administered to a horse under the care or control of a Licensed Trainer or Permitted Trainer must be kept by the trainer for a period of not less than one year. 13.2 Each record must include at least the following information 13.2.1 date of commencement and prescribed duration of any Treatment, 13.2.2 name of the horse, 13.2.3 name of the Treatment used, 13.2.4 route and dosage per day of the Treatment, 13.2.5 name of the Person administering the Treatment, 13.2.6 name of the Person authorising or prescribing the Treatment. 13.3 The records must be made available for inspection 13.3.1 by any approved Person authorised to enter the trainer's premises under Part (A)5, and 13.3.2 in accordance with any directions given by the Authority when conducting an enquiry under that Part of that Manual into a possible contravention of these Rules. 13.4 Treatment means any medication or treatment containing a Prohibited Substance administered to a horse under the care of a Licensed Trainer or Permitted Trainer whether or not currently in training. What do trainers have to do?

7. Trainer/vet working • Traditional situation of one vet per trainer, with unwritten understanding that both are acting within the Rules? • This has changed – inter-vet competition, commercial pressures on both, availability of medicines on-line/from others, increasing trend in trainers to use one vet for one thing and another for another; owner pressures/preferences for veterinary services • It’s not easy! • The BHA work to increase information/access available to vets so that they can be informed directly themselves about what is required of their clients • Collaborating on this with BEVA /ARVS • Options may include formalisation of the working relationship between trainers and their vets; Memorandums of Understanding/Contracts/Guides for Vets drawn up by BHA/BEVA/ARVS/NTF …in the meantime…..

8. When do equine vets come across theBHA in the context of medication? • When a trainer has a positive post race sample – often at interview with the Integrity Department, depending on the case a BHA vet will also be there • Proactive contact to try to find out when a drug should be withdrawn before raceday: BHA advises on Detection Times where possible/where not, still endeavours to give advice based on whatever information we have (access to) • Proactive contact to discuss electively testing a horse before an engagement to run where a mistake may have been made/horse is new to the yard etc. • Testing in training, when there is a query or mismatch with what has been recorded in the Medication Record and what has been found in the horse • Other reasons to seek information, eg assistance with legal cases, drug advice in general, eg http://www.britishhorseracing.com/resources/equine-science-and-welfare/medication-control-research.asp

9. Practicalities: what leads to a positive? • Prohibited substance – anything which has an effect on a body system • Laboratories do not look for specific substances in the samples they receive from us • Instead, ‘A’ samples are ‘screened’ against a library of 1000’s of substances (usually using mass spec) • If there is a possible ‘match’, then the sample is re-run; ‘confirmatory’ analysis • If this is positive then the ‘A’ sample is reported positive, and an investigation initiated • The ‘B’ sample may be subject to ‘counter analysis’ – at the trainer’s choice • A Disciplinary Panel then considers the case once the investigation is complete, often with legal counsel for both sides

10. Practicalities: Detection Times • Basis of DTs is that they relate to a concentration of drug at screening that does not have a clinical effect, calculated from ‘no effect’ levels (Pierre Louis Toutain – see ehslc.com). This is not the same as a threshold – which relies on full quantification • 3 stages to their definition – risk analysis (data generation, excretion curves); risk assessment (interpretation of data); risk communication • These stages are agreed internationally, in order to ensure pooling of resources, avoidance of unnecessary animal experiments and ultimately harmonisation of screening levels, and DTs where possible • This has to date been within the EHSLC but increasingly now involves the Asian Racing Federation and the (American) Racing and Medication Testing Consortium (RMTC)/individual US regulatory authorities

11. International Screening Limits And Detection Times

12. Practicalities: Research

13. First year - 14 studies ‘Doping’ Herbal diuretic ‘milkshaking’ anabolic steroid Detection Time Studies Prednisolone ‘Sedalin’, ACP ‘Flixotide’, fluticasone ‘Domosedan Gel’, detomidine Other Devil’s Claw Post gelding series of samples as reference Urine, blood, hair and saliva as matrices Centre for Racehorse Studies 2010 13 Photographs courtesy of Rebecca Milmine

14. 15 studies in 2011 ‘Doping’ None to date.... Detection Time Studies ‘Pulmicort’ (budesonide) ‘Ventolin’ (salbutamol) ‘Serevent’ (salmeterol) ‘Domosedan/Torbugesic’ ‘Flixotide’ (high dose fluticasone) Probably dantrolene (‘Dantrium’) Centre for Racehorse Studies 2011 Photographs courtesy of Rebecca Milmine 14

15. Practicalities: DTs/Interpretation of data • Up until now the drugs studied have been intravenously administered (and therefore suitable for the model) or there have been adequate ‘no effect’ data available – eg for mepivacaine • We are now facing more challenging issues • relating to complex PK/PD questions • combinations of drugs • How to relate systemic concentrations of locally administered, potent, medications – in particular inhaled and intra-articular – to effect • These may call for different approaches, • PK/PD workshop this October • ‘Standstill’ approaches – GBGB, 7 days; Nordic countries, 28 days • the ‘14 day Rule’ with regard to intra-articular corticosteroids – France introducing this autumn • These in turn will require a range of approaches to sampling/regulating

16. Practicalities: ‘Flexible testing’

17. Pre- race testing is necessary to detect /deter the administration of alkalinising agents, ‘milkshaking’ – first UK case in 2007 New approachbased on using a handheld iSTATanalyser - to screen then direct possible further sampling Work at the BHA’s Centre for Racehorse Studies has correlated data from this with the ‘gold standard’ (Beckman ELISE) back at HFL If at or above an action level, horse detained for a regulatory sample 2 hours after its run Flexible testing – Pre Race Testing

18. Usually an educative approach unless there is specific intelligence • Veterinary Officer allocates the number of tests according to an assessment of medication use, recording, previous history etc • Samples are screened at full sensitivity • Results are used to direct further testing, analysis and, importantly, feedback to trainer • Medication records are crucial for both vets and trainers – in the event of positive findings, a proper record allows proper evaluation – eg ‘near misses’, yard contamination Flexible testing - Testing in Training

19. Practicalities: Elective Testing • Intended for agents with long duration of action/accidents • Horse must be entered to run • Testing for one specified drug with defined record of administration • Has to be authorised by the BHA • Costs ~ £100 – aim for result in 48 hours

20. In conclusion…. • Drug testing is more complex than ever before • It is an international activity which is becoming increasingly harmonised • It is based on protecting the horse and jockey, and giving confidence to the general and betting public • A high priority is providing advice for veterinary surgeons