1. -Point- The Quest for Clean Competition in Sports: Are We the Dopes? G.S. Baird October 2014 www.clinchem.org/content/60/10/1276.full © Copyright 2014 by the American Association for Clinical Chemistry

2. © Copyright 2009 by the American Association for Clinical Chemistry Introduction  Doping is variably prevalent amongst athletes, yet there are high-profile cases of elite athletes who are caught, and some survey data to suggest that the prevalence is quite high in specific cohorts  Undoubtedly there is some deterrent effect from antidoping measures, but getting caught is still unlikely, and the potential benefit from doping appears to be high (although this is admittedly controversial).  Elite athlete dopers have more resources (and highly capable analytical laboratories) at their disposal.

3. © Copyright 2009 by the American Association for Clinical Chemistry Questions on Antidoping Testing  Why do we test athletes for performance- enhancing drugs? Why should we? Safety? Fairness?  Has antidoping testing made sports safer and fairer?  Does the public understand the limitations of the tests that clinical chemists do to detect doping?  Can a deterrence scheme be effective if it misses a high percentage of offenders?

4. © Copyright 2009 by the American Association for Clinical Chemistry Figure 1. The pre- and post-test probabilities from laboratory tests given various test specifications (sensitivity/specificity) and results (positive/negative). Posttest probabilities tend towards 0 or 1 for negative and positive results, respectively, across a wide range of pretest probabilities when sensitivity and specificity are both high (blue and green curves); this means that results are often interpretable. When the test is made highly specific but poorly sensitive, as anti- doping tests frequently are (red and purple curves), positive results are interpretable albeit uninformative if pretest probability is already high, and negative results are difficult to interpret because pretest probability is very close to posttest probability. Test Efficiency from Bayes’ Theorem

5. © Copyright 2009 by the American Association for Clinical Chemistry What would happen if we stopped?  In the absence of any deterrence, rates of doping would be expected to increase, but what if they are already close to 100%?  A playing field that is permissive to doping is not “fair”, but is it “fair” now?  The entire problem comes down to what we expect, as a society, from our athletes, especially the professional ones. This might best be discussed in social studies classrooms, not clinical chemistry journals.  The financial motivations present in sport today may make meaningful changes impossible.

6. -Counterpoint- The Quest for Clean Competition in Sports: Deterrence and the Role of Detection L.D. Bowers October 2014 www.clinchem.org/content/60/10/1279.full © Copyright 2014 by the American Association for Clinical Chemistry

7. © Copyright 2009 by the American Association for Clinical Chemistry What is the objective of an anti-doping program?  Deter individuals from making the decision to use performance-enhancing substances  Ensure compliance with rules made to create a level playing field for true competition  Pharmacological anarchy does not result in a level playing field. Imagine two individuals – one with a hematocrit (Hct) of 42 and one with an Hct of 48. If both increase their Hct to 50, the first individual gets more of a performance enhancement.  Athletes could be coerced into participating in unregulated human experimentation.

8. © Copyright 2009 by the American Association for Clinical Chemistry Compliance with Rules  Moral inhibitions are the most important factor in an individual’s decision to comply with a rule Compliance with the rule is viewed as a duty (deontological ethics)  Moral inhibitions can be re-enforced by a community of athletes that actively supports an anti-doping creed or statement  Moral inhibitions are weakened by isolation from the community and rationalization  Moral inhibitions do not always correlate with behavior  When moral inhibitions are weak, deterrence strategies can be used to ensure compliance with a rule

9. © Copyright 2009 by the American Association for Clinical Chemistry Factors that Impact Deterrence  Perceived certainty of being caught  Collection strategies must increase athlete certainty about being caught (“ambiguity avoidance”) −No-advance notice −Out-of-competition vs. in-competition collections  New testing methods and strategies −Testing changes athlete behaviors (e.g., route of administration), which requires new tests −New therapeutic agents with abuse potential require research into new tests

10. © Copyright 2009 by the American Association for Clinical Chemistry Factors that Impact Deterrence  Perceived severity of the penalty  Formal sanctions −Penalties imposed by the governance structure (e.g., 2 years of ineligibility)  Informal sanctions −“Costs” imposed by significant others (e.g., loss of reputation, etc)  Perception of the “quickness” (celerity) of the imposition of the sanction  Delaying the sanction is perceived as beneficial by the individual breaking the rule  The time required to prepare a reasonable defense must be balanced with importance of the celerity of the sanction

11. © Copyright 2009 by the American Association for Clinical Chemistry Strategies increasing certainty of detection  Intra-individual reference ranges  Sequential blood and urine samples allow prediction of expected range within which the next result should fall  Some values are expected to be “negative”  Alternate sample matrices  Oral fluid and dried blood/plasma spots could result in more cost-effective collections  Development of new test methods  Development of tests like LC-MS/MS method for IGF-1 and hCG helps clinical and endocrinology fields as well as anti-doping  Collection of non-analytical data on individual doping practices (e.g., purchase of doping products)

12. © Copyright 2009 by the American Association for Clinical Chemistry Summary  The most important factor in rules compliance is moral inhibitions  The principles of perceptual deterrence provide a strategy for maximizing deterrence  Certainty  Severity  Celerity  Increased certainty of detection requires research into new testing methods and strategies that benefits a range of scientific disciplines, including clinical chemistry

13. © Copyright 2009 by the American Association for Clinical Chemistry Thank you for participating in this month’s Clinical Chemistry Journal Club. Additional Journal Clubs are available at www.clinchem.org Download the free Clinical Chemistry app on iTunes for additional content! Follow us