Bioethics and ‘big pharma ’ Rebecca Kukla, Georgetown University

1. Bioethics and ‘big pharma’Rebecca Kukla, Georgetown University Kennedy Institute of Ethics Intensive Bioethics Course, Summer 2014

2. Key features of pharmaceutical companies: • They are for-profit companies – primary interest is profit, stakeholders not bound by Hippocratic oath. • They are mostly multinational – operate across borders and cultures, not bound by the rules or constraints of any one country. • Vast amount of money and (hence) lobbying power. Can take huge risks and absorb huge losses.

3. We will look at influence on • Research • What gets researched • Research methodology • Communication of research results • Clinical practice • What counts as a disease

4. Influence of ‘Big Pharma’ on Research: What gets research attention? • The ‘neglected disease’ problem: • Developing world: 80% of population, 20% of medicine • 10% of research devoted to conditions with 90% of global disease burden • Over 25 recent years: 1400 new drugs, <1% for tropical diseases • $100 million/year worldwide spent on tropical disease research vs. over $3 billion/year in US alone for cancer research.

5. Influence of ‘Big Pharma’ on Research: What gets research attention? • TRIPS and patent system keep problem in place. • Designed to protect and create a (relatively) free, profitable market in intellectual property. • Patents for 20 years, with various exceptions/limitations. • Prevents companies from making generics at low prices; gives original company a monopoly on prices. SO no motive to develop anything that will have to be cheap.

6. Influence of ‘Big Pharma’ on Research: What gets research attention? • TRIPS and patent system keep problem in place. • What kind of research does patent system stimulate? • Drugs for conditions of the wealthy, especially for conditions that can be marketed as wide-spread (regardless of seriousness) – depression, cosmetic products. • ‘Me too’ drugs offering little to no clinical advantage – minimal new research gives market share of popular products – depression, erectile dysfunction. • One estimate: one in three drugs patented in last 25 years represents a therapeutic advance.

7. Influence of ‘Big Pharma’ on Research: Research Methodology • Research is always governed by values and interests. • Pharmaceutical-funded research shaped by specific values/interests: profit, patentability, marketability, image of company, framing of a disease… • Values/interests can create bias when they distort the objectivity of the research. • BUT I am more interested in cases where values/interests shape research without making it ‘bad science’ – not biased or distorted in classic sense.

8. Inductive risk • We all know that values enter into what we study, how we study it, how we use results. • Rudner 1953: The scientist qua scientist makes value judgments! • Science is inherently probabilistic and inference is always uncertain. • Must trade off risk of false positives and risk of false negatives in accepting or rejecting a hypothesis. • This is always inherently value laden and interest relative – no objective, value-independent answer to how certain we need to be before accepting a hypothesis.

9. Richard Rudner 1953: “If the hypothesis under consideration were to the effect that a toxic ingredient of a drug was not present in lethal quantity, we would require a relatively high degree of confirmation or confidence before accepting the hypothesis - for the consequences of making a mistake here are exceedingly grave by our moral standards. On the other hand, if say, our hypothesis stated that, on the basis of a sample, a certain lot of machine stamped belt buckles was not defective, the degree of confidence we should require would be relatively not so high. How sure we need to be before we accept a hypothesis will depend on how serious a mistake would be.”

10. Response to Rudner “Hypothesis acceptance/rejection is not part of science – it comes at the end. Scientists should just give degrees of confirmation in light of the evidence. It is only in decisions about whether or not to act on the basis of a given hypothesis that value-judgments about possible consequences of errors come into play.” (Richard Jeffrey 1956)

11. Values all the way down • Douglas 2000: • There are interest-driven inductive risk decisions throughout the scientific process – We can’t ‘purify’ science. • Classifying data in dioxin studies • Methodological choices in Bisphenol A studies • Deciding what counts as usable data in NSAID studies

12. Influence of ‘Big Pharma’ on Research: Research Methodology The point: interests of pharmaceutical industry will shape the inductive risk balancing in ways that don’t necessarily align with traditional ends of medicine, patient interests, public good. And there is no getting away from this!

13. Influence of ‘Big Pharma’ on Research: Communication of Research Results • Publications often put together by teams of insiders, ghostwritten. • Names of prominent researchers are added later. • Often, ‘authors’ have no access to raw data and no part in research process. • This is made possible by watered-down requirements for authorship in age of massive collaboration.

14. Influence of ‘Big Pharma’ on Research: Communication of Research Results • 2000 lawsuit against Pfizer (Motus v Pfizer) • Made public internal memos on state of 85 articles on Sertraline (Zoloft) commissioned from ghostwriting company (Current Medical Directions).

15. Publications on studies of Sertraline over three years:

16. Influence of ‘Big Pharma’ on Research: Communication of Research Results • Other media of communication of health information shaped by industry interests: • Pharma-funded continuing education workshops • Information sheets for clinicians • Direct to consumer advertising • Etc.

17. Influence of ‘Big Pharma’ on Research: Communication of Research Results • Of course such materials are shaped by profit interests – that’s not what’s ethically or epistemologically interesting. • The problem: Reach of pharma into all info delivery goes deep enough that there’s no good way to sort out the ‘pure’ info. • Complex, overlapping, multitudinous sources of health information make pathway tracking nearly impossible. • The line between scientific communication and marketing is hopelessly skewed in practice.

18. The example of BiDil

19. The example of BiDil

20. Influence on Clinical Practice

21. Influence on Clinical Practice • In addition to advertising, Pharma has representatives at every stage of the process of determining standards of care... • Industry insiders and people with industry financial ties: • Testify at FDA hearings and sit on FDA approval committees. • Sit on committees that write care guidelines. • Give media interviews about drugs, often with no notation of conflict of interest.

22. Influence on Clinical Practice • Brody and Light: “Inverse Benefit Law”: • Pharma has motive to lower threshold for drug prescription. • Generally, drugs give most benefit to those with more severe symptoms/conditions. • Adverse side effects are random. • THUS lowering prescribing threshold increases harm more than it increases benefit.

23. Influence on Clinical Practice • Pharmaceutical industry involvement at all levels of research and care has created a culture that reconceives illness as need for drugs, and healthy bodies as either ill or ‘at risk’. • ‘Polypharmacy’: >5 prescriptions. This has increased 6-fold since 1990. • Multiple prescriptions are expensive, make adverse reactions more likely, and tend to cascade. • Prescriptions replace emphasis on lifestyle changes. • Lowered thresholds create a culture of illness, medical intervention, and risk. • DTC marketing/“Ask your doctor”… calls us to conceive of ourselves as people with drug-treatable conditions. • Ad emphasis on identity/lifestyle helps shift self-conceptions.

24. What Counts as a Disease? Medicalization: • Medical professionals as managers of and experts on condition. • Diagnosis through examination of single bodies in clinics. • Disorder is located in an organ or system of body; it’s the kind of thing that can be cured or mitigated through targeted intervention such as drugs or surgery, • Disorder is not a matter of morality or character.

25. What Counts as a Disease? • Pharma industry has a strong interest in medicalizing. • Pharma plays a role in multiplying and broadening disease categories: • ‘At risk’ categories like ‘pre-hypertensive’ • Lowered thresholds • Medicalization of personality traits or lifestyle conditions like sexual dissatisfaction, shyness, obesity • Investment particularly in chronic conditions • Medicalization can involve serious shifts in how we think of disease, how people understand body, identity. • Identity as a patient with a diagnosis and need for intervention/management has far-reaching consequences.

26. What Counts as a Disease? Objection: but if these drugs work, aren’t they really treating diseases? • Lots of conditions can be improved somewhat by drugs but that doesn’t mean it’s the best way to conceptualize them or the best approach to mitigating them. • Looping effects: being categorized (as ADHD, pre-hypertensive, sexually dysfunctional, depressed) changes behavior, self-conception, treatment by others – helps make reality, doesn’t just reflect it.

27. Case Study in Disease Generation: Erectile Dysfunction

28. Case Study in Disease Generation: Erectile Dysfunction

29. Further Reading: • Justin Biddle, “Lessons from the Vioxx Debacle: What the Privatization of Science Can Teach Us About Social Epistemology”, Social Epistemology 21(1), 2007. • Howard Brody, Hooked! Ethics, the Medical Profession, and the Pharmaceutical Industry, Rowman and Littlefield 2007. • Peter Conrad, The Medicalization of Society: On the Transformation of Human Conditions into Treatable Disorders, Johns Hopkins University Press, 2007. • Doctors without Borders, “Fatal Imbalance: The Crisis in Research and Development for Drugs for Neglected Diseases”, 2001. • Heather Douglas, “Inductive Risk and Values in Science”, Philosophy of Science 67(4), 2000. • David Healy and Dinah Cattell, “Interface between Authorship, Industry, and Science in the Domain of Therapeutics:, British Journal of Psychiatry 183, 2003. • Rebecca Kukla, “Author TBD: Radical Collaboration in Contemporary Biomedical Research”, Philosophy of Science 79(5), 2012. • Joel Lexchin, “Bigger and Better: How Pfizer Redefined Erectile Dysfunction”, PLOS Medicine, April 2006. • Pamela Sankar and Jonathan Kahn, “BiDil: Race Medicine or Race Marketing?”, Health Affairs, 2005.