Pharmageddon

by David Healy

  CHAPTER 3

  1. Jason Dana and George Loewenstein, A social science perspective on gifts to physicians from industry, JAMA 290: 2, 252–255 (2003).

  2. Michael A. Steinman, Michael G. Shlipak, and Steven J. McPhee, Of principles and pens: Attitudes of medicine house staff toward pharmaceutical industry promotions, American Journal of Medicine, 110, 551–557 (2001).

  3. Meredith Wadman, The senator's sleuth, Nature 461, 330–33 (Sept. 17, 2009).

  4. James Lind, A Treatise of the Scurvy (1752; Edinburgh: Edinburgh University Press, 1953), 145.

  5. Philippe Pinel, Traité médico-philosophique sur la manie (1800), trans. D. Davis (London: Cadell and Davies, 1806).

  6. Philippe Pinel, Traité médico-philosophique sur l'aliénation mentale (1809), trans. Gordon Hickish, David Healy, and Louis C. Charland (Chichester: John Wiley and Sons, 2009).

  7. Pierre C. A. Louis, cited in A. M. Lilienfeld, Ceteribus paribus: The evolution of the clinical trial, Bulletin of the History of Medicine 56, 1–18, 6 (1982).

  8. Pierre C. A. Louis, cited in M. D. Rawlins, Development of a rational practice of therapeutics, BMJ 301, 729–733 (1990).

  9. L. M. Lawson (1849), cited in Charles E. Rosenberg, “The therapeutic revolution: Medicine, meaning and social change in nineteenth-century America,” in The Therapeutic Revolution, ed. M. J. Vogel and C. E. Rosenberg, 20 (Philadelphia: University of Pennsylvania Press, 1979).

  10. Rabies turned out to be caused by a virus rather than a bacterium.

  11. Roy Porter, The Greatest Benefit to Mankind (London: Fontana Press, 1999).

  12. Martha Marquardt, Paul Ehrlich (New York: Henry Schumann, 1951).

  13. Paul De Kruif, Microbe Hunters (New York: Harcourt, 1926).

  14. Sandra Hempel, The Strange Case of the Broad Street Pump: John Snow and the Mystery of Cholera (Berkeley: University of California Press, 2009).

  15. Lawrence Altman, Who Goes First? The Story of Self-Experimentation in Medicine (New York: Random House, 1987).

  16. Sanjeebit J. Jachuk, H. Brierley, S. Jachuk and P. M. Willcox, The effect of hypotensive drugs on the quality of life, Journal of the Royal College of General Practitioners 32, 103–105 (1982).

  17. Ronald Fisher, The Design of Experiments (Edinburgh: Oliver and Boyd, 1935).

  18. Steven T. Ziliak and Deirdre N. McCloskey, The Cult of Statistical Significance: How the Standard Error Cost Us Jobs, Justice and Lives (Ann Arbor: University of Michigan Press, 2008).

  19. A phrase widely attributed to Charlie Poole.

  20. Gordon C. Smith and Jill P. Pell, Parachute use to prevent death and major trauma related to gravitational challenge, BMJ 327, 1459–1461 (2003).

  21. Thomas Hager, The Demon under the Microscope (New York: Harmony Books, 2006).

  22. Philip J. Deveraux and the POISE Study Group, Effects of extended release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): A randomized controlled trial, Lancet 371 (2008), doi:10.1016/S0140–6736(08) 60601–7.

  23. Marc A. Pfeffer, Emmanuel A. Burdmann, Chao-Yin Chen et al., A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease and anemia, NEJM 361 (2009), doi:10.1056/NEJMoa0907845; Philip A. Marsden, Treatment of anemia in chronic kidney disease: Strategies based on evidence, NEJM 361 (2009), doi:10.1056/NEJMe0909664.

  24. Bruce M. Psaty and Richard A. Kronmal, Reporting mortality findings in trials of rofecoxib forAlzheimer disease or cognitive impairment, JAMA 299, 1813–1817 (2008).

  25. Harry Collins and Trevor Pinch, Dr. Golem. How to Think about Medicine (Chicago: University of Chicago Press 2005).

  26. Mary Robertson and Michael Trimble, Major tranquilizers used as antidepressants, J Affective Disorders 4, 173–193 (1982).

  27. David Healy, Let Them Eat Prozac (New York: New York University Press, 2004).

  28. The data for this figure stem from the FDA's review of antidepressants drugs. M. Stone and L. Jones, Clinical Review (2006), 31; http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006–4272bi-index.htm.

  29. Neither the data nor the arguments here apply to severe cases of depression in secondary care, melancholia for instance. This works to the advantage of companies, who can portray the much smaller placebo response in melancholia as good evidence that antidepressants do in fact work.

  30. David Healy, The assessment of outcome in depression: Measures of social functioning, Reviews in Contemporary Pharmacotherapy 11, 295–30! (2000).

  31. Daniel Kahnemann, Paul Slovic, and Amos Tversky, Judgment under Uncertainty: Heuristics and Biases (Cambridge: Cambridge University Press, 1982).

  32. ALLHAT (The antihypertensive and lipid-lowering treatment to prevent heart attack trial), Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs. diuretic, JAMA 288, 2981–2997 (2002).

  33. Healy, Let Them Eat Prozac.

  34. Joseph F. Wernicke et al., Low-dose fluoxetine therapy for depression, Psychopharmacology Bulletin 24, 183–188 (1988).

  35. Jean Thuillier, Ten Years that Changed the Face of Mental Illness, trans. Gordon Hickish (London: Martin Dunitz, 1999).

  36. David J. Osborn et al., Relative risk of cardiovascular and cancer mortality in people with serious mental illness from the United Kingdom's General Practice Research Database, Archives of General Psychiatry 64, 1123-1131 (2007); Sukanta Saha, David Chant, and John McGrath, A systematic review of mortality in schizophrenia, Archives of General Psychiatry 64, 1123-1131 (2007).

  37. Archibald Cochrane, Effectiveness and Efficiency (London: Nuffield Provincial Hospitals' Trust, 1972).

  38. “Percentage of practice that is evidence based” (Sheffield University website): http://www.shef.ac.uk/scharr/ir/percent/html (accessed Oct. 30, 2009).

  39. Iain Chalmers, Kay Dickerson, and Thomas C. Chalmers, Getting to grips with Archie Cochrane's Agenda, BMJ 305, 786–788 (1992).

  40. David L. Sackett, Brian R. Haynes, Gordon Guyatt, and Peter Tugwell, Clinical Epidemiology: A Basic Science for Clinical Medicine (Boston: Little Brown, 1985); David L. Sackett and William M. Rosenberg, The need for evidence-based medicine, Journal of the Royal Society of Medicine 88, 620–624 (1995).

  41. David Healy and Marie Savage, Reserpine exhumed, British Journal of Psychiatry 172, 376–378 (1998).

  42. David L. Davies and Michael Shepherd, Reserpine in the treatment of anxious and depressed patients, Lancet 117–121 (1955).

  43. Michael Shepherd, “Psychopharmacology: Specific and non-specific,” in The Psychopharmacologists, ed. David Healy, 2, 237–257 (London: Arnold, 1998).

  44. F. Horace Smirk and E. Garth McQueen, Comparison of rescinamine and reserpine as hypotensive agents, Lancet 115–116 (1955); Douglas C. Wallace, Treatment of hypertension. Hypotensive drugs and mental changes, Lancet 116–117 (1955).

  45. Martin H. Teicher, Carol Glod, and Jonathan O. Cole, Emergence of intense suicidal preoccupation during fluoxetine treatment, American Journal of Psychiatry 147, 207–210 (1990).

  46. Charles Medawar and Anita Hardon, Medicines Out of Control? (Amsterdam: Aksant, 2004).

  47. Austin Bradford Hill, Reflections on the controlled trial, Annals of the Rheumatic Diseases 25, 107–113 (1966).

  CHAPTER 4

  1. These include commercial/financial, legal, and patent departments, as well as the relatively separate manufacturing operations.

  2. CenterWatch, State of the Clinical Trials Industry (Boston: CenterWatch, 2009).

  3. Kurt Eichenwald and Gina Kolata, “A doctor's drug studies turn into fraud,” New York Times, May 17, 1999; Steve Stecklow and Laura Johannes, “Questions arise on new drug testing. drug makers relied on clinical researchers who now await trial,” Wall Street Journal, Aug. 15, 1997; Carl Elliott, “Guinea pigging. Healthy human subjects for drug safety trials are in demand. But is it a living?” New Yorker, 36–41, Jan. 7, 2008.

  4. E-mail from Ian Barton to Richard Eastell and Aubrey Blumsoh
n, cc M. Royer, April 24, 2003.

  5. Aubrey Blumsohn, Authorship, ghost-science, access to data and control of the pharmaceutical scientific literature—who stands behind the word? American Association for the Advancement of Science Professional Ethics Reports 19 (Summer 2006), http://www.aaas.org/ssp/sfr1/per/per46.pdf.

  6. Claire Dyer, Aubrey Blumsohn: Academic who took on industry, BMJ 340, 22–23 (2010).

  7. Rather than break the law, companies use strategies such as distinguishing between parent and local companies or company-initiated and investigator-initiated studies—conveniently some of the most awkward results may lie in studies that can be defined as other than company studies.

  8. Names include Alliance, Adis Communications, Alpha-Plus, Axis Healthcare Communications, ClinResearch, Complete Healthcare Communications, Current Medical Directions, Envision Pharma, Evolution Medical Communications, Excerpta Medica, Gardiner-Caldwell, GYMR, HealthCare Project Management, Heron Evidence Development, IntraMed, Lowe Fusion Healthcare, MedBio Publications, Medical Writes, MSource Medical Development, Pacific Communications, Pharmanet, Ruder Finn, Scientific Therapeutics Information, Synapse Medical Communications, Thompson Scientific Connections, Watermeadow Medical, and Wolters Kluwer Health.

  9. WPP stands for Wire and Plastics Products PLC. But it has moved so far from its original business, to being the largest advertising agency in the world, that it is only called WPP today.

  10. From GYMR website (accessed Feb. 25, 2004).

  11. David Healy, Let Them Eat Prozac (New York: New York University Press, 2004).

  12. There are recognized quality measures for reporting the results of RCTs including, for instance, specifying the randomization procedures and the primary endpoints of the original trial protocol. In blind assessments of the reports of trials run by industry compared to independent studies, those done by industry rate higher. When it comes to box ticking, medical writers are specialists in the exercise where academics are not.

  13. Bruce M. Psaty and Richard A. Kronmal, Reporting mortality findings in trials of rofecoxib for Alzheimer disease or cognitive impairment, JAMA 299, 1813–1817 (2008).

  14. Catherine DeAngelis and Phil B. Fontanarosa, Impugning the integrity of medical science: The adverse effects of industry influence, JAMA 299, 1833–1836 (2008).

  15. See http://www.healyprozac.com for the entire document.

  16. Armen Keteyian, “Suicide epidemic among veterans,” CBS News Investigates, Nov. 13, 2007, http://www.cbsnews.com/stories/2007/ii/13/cbsnews_investigates/main3496471.shtml. A CBS news investigation uncovers a suicide rate for veterans twice that of other Americans.

  17. See http://www.healthyskepticism.org/presentations/2007/Study329.ppt (accessed Sept. 1, 2010).

  18. Jon Jureidini, Leemon B. McHenry, and Peter R. Mansfield, Clinical trials and drug promotion: Selective reporting of Study 329, International Journal of Risk and Safety in Medicine 20, 73–81 (2009).

  19. Alison Bass, Side Effects (Chapel Hill, NC: Algonquin Books, 2008).

  20. Martin D. Keller, Neal D. Ryan, and Michael Strober et al., Efficacy of paroxetine in the treatment of adolescent major depression: A randomized, controlled trial, Journal of the American Academy of Child and Adolescent Psychiatry 40, 762–772 (2001).

  21. See http://www.healthyskepticism.org/presentations/2007/Study329.ppt.

  22. E-mail from Sally Laden to Daniel Burnham re Par 222 manuscript, Dec. 14, 2000.

  23. Louis Sulman, Certain conditions in which a volatile vasoconstrictor has proved of particular value—A preliminary report, Medical Times 63, 374–375(1935).

  24. Nicholas Rasmussen, On Speed: The Many Lives of Amphetamine (New York: New York University Press, 2008).

  25. Rasmussen, On Speed.

  26. Rasmussen, On Speed.

  27. Soma Weiss, Chemical structure: biological action: therapeutic effect, NEJM 220, 906–911 (1939).

  28. Rasmussen, On Speed.

  29. Louis Lasagna, “Back to the future: Evaluation and drug development 1948–1998,” in The Psychopharmacologists, ed. David Healy, 2, 135–166 (London: Arnold, 1998).

  30. Sandra Hempel, The Strange Case of the Broad Street Pump: John Snow and the Mystery of Cholera (Berkeley: University of California Press, 2009).

  31. Robert Whitaker, Anatomy of an Epidemic (New York: Crown Publishers, 2010).

  32. David Michaels, Doubt Is Their Product (New York: Oxford University Press, 2008).

  33. Michaels, Doubt Is Their Product.

  34. James Turk and Jon Thompson, Universities at Risk: How Politics, Special Interests and Corporatization Threaten Academic Integrity (Toronto: Lorimer Press, 2008).

  35. Jason Lazarou, Bruce H. Pomeranz, and Paul N. Corey, Incidence of adverse drug reactions in hospitalized patients: A meta-analysis of prospective studies, JAMA 279, 1200–1205 (1998).

  36. Charles M. Beasley et al., Fluoxetine and suicide: A meta-analysis of controlled trials of treatment for depression, BMJ 303, 685–692 (1991).

  37. Ian Oswald, Letter, BMJ 303, 1058 (1991).

  38. All correspondence is available on http://www.healyprozac.com.

  39. M. N. Graham Dukes and Barbara Schwartz, Responsibility for Drug-Induced Injury (New York: Elsevier, 1988).

  40. David Healy, Guest Editorial: A Failure to Warn, International Journal of Risk and Safety in Medicine 12, 151–156 (1999).

  41. David Healy, Emergence of antidepressant-induced suicidality, Primary Care Psychiatry 6, 23–28 (2000).

  42. Carl Elliott, Introduction, in Prozac as a Way of Life, ed. Carl Elliott and Tod Chambers (Durham, NC: Duke University Press, 2004). The original articles were P. Kramer, The valorization of sadness: Alienation and melancholic temperament, Hastings Center Report 30, 13–19 (2000); C. Elliott, Pursued by happiness and beaten senseless: Prozac and the American Dream, Hastings Center Report 30, 7–12 (2000); D. DeGrazia, Prozac, enhancement and self-creation, Hastings Center Report 30, 34–40 (2000); J. C. Edwards, Passion, activity and “the care of the self,” Hastings Center Report 30, 31–33 (2000); D. Healy, Good science or good business? Hastings Center Report 30, 19–22 (2000).

  43. Cited in Elliott, Introduction, in Prozac as a Way of Life.

  44. David Healy and Dinah Cattell, The Interface between authorship, industry and science in the domain of therapeutics, British Journal of Psychiatry 182, 22–27 (2003).

  45. Aubrey Blumsohn, http://scientific-misconduct.blogspot.com(accessed Sept. 25, 2006).

  46. The full letter read: “The report by the pharmaceutical industry was replete with exhortations that we should recognise the partnership industry have with academia. But it is difficult to know what kind of partnership you can have with an organisation that breaches the fundamental norms of science and threatens to sue those who point this out. Readers should be in little doubt that THES, the Lancet and BMJ soft-pedal on publication of issues like this on the counsel of their lawyers. At a recent Royal College meeting on conflict of interest, when College members expressed concern about industry suppression of data among other things, an industry spokesperson asked those assembled how Britain's leaders in that particular academic field, the 25 professors who, over and above their salaries, earned more than £150,000 per annum from links to industry, would view proposals to control conflict of interest. He also invited the College to take into account the fact that 40% of life assurance policies were invested in pharmaceutical shares and that anything that hurt industry would be bad for doctors. Where once medicine and the pharmaceutical industry were beating a way upstream in efforts to remedy some of humanity's real afflictions, industry turned into the current some years ago, dragging medicine back with it. In the process patients have been deserted in favour of a far greater number of consumers who could be super-sized on drugs they don't need for conditions like osteoporosis—if only the ‘science' can be used to scare people into consuming. This new pharmaceutical industry would no more welcome a real partnership with science than would the fast-food or tobacco
industries.”

  47. Jon Jureidini, Leemon B. McHenry, and Peter R. Mansfield, Clinical trials and drug promotion: Selective reporting of Study 329, International Journal of Risk and Safety in Medicine 20, 73–81 (2009). See also Melanie Newman, The rules of retraction, BMJ 341, 1246–1248 (2010).

  48. David Healy, Did regulators fail over selective serotonin reuptake inhibitors? BMJ 333, 92–95 (2006).

  49. Catherine De Angelis, The influence of money on medical science, JAMA 296, 996–998 (2006).

  50. Cathyrn Clary, Zoloft: Publications Steering Committee Update (July 27, 2000); document made available in Szybinski Case, available from the author.

  51. David Healy and Dinah Cattell, The Interface between authorship, industry and science in the domain of therapeutics, British Journal of Psychiatry 182, 22–27 (2003).

  52. L. Duggan et al., Olanzapine for schizophrenia, Cochrane Database of Systematic Reviews Issue 2 (2005), art. no.: CD001359, doi:10.1002/14651858 .CD001359.pub2.

  53. Clary, Zoloft: Publications Steering Committee Update.

  54. American College of Neuropsychopharmacology, Preliminary report of the task force on SSRIs and suicidal behavior in youth, Neuropsychopharmacology 31, 473–492 (2006).

  55. Gary D. Tollefson et al., Absence of a relationship between adverse events and suicidality during pharmacotherapy for depression, Journal of Clinical Psychopharmacology 14, 163–169 (1994); Andrew Leon et al., Prospective study of fluoxetine treatment and suicidal behavior in affectively ill subjects, American Journal of Psychiatry 156, 195–201 (1999); Charles B. Nemeroff, Michael T. Compton, and Joseph Berger, The depressed and suicidal patient: Assessment and treatment, Annals of the New York Academy of Science 932, 1–23 (2001).

  56. Kimberly A. Yonkers et al., The management of depression during pregnancy: A report from the American Psychiatric Association and the American College of Obstetricians and Gynecologists, General Hospital Psychiatry 31, 403–413 (2009).