Restoring Study 329

Scientific Integrity Through Data Based Medicine

Children of the Cure

References

Chapter 3

  1. For references supporting the portrait painted here see Healy, D. The Antidepressant Era. (Harvard University Press, Cambridge Ma 1997); and Healy, D. The Creation of Psychopharmacology, (Harvard University Press, Cambridge Ma 2002).
  2. Smith MC, A Social History of the Minor Tranquilizers (New York: Haworth Press, 1991).
  3. Medawar C. Interview on study329.org
  4. Lader M, interview on study329.org
  5. Ayd F. Interview on study329.org
  6. Delini-Stula A, Interview on study329.org; Waldmeir P, Interview on study329.org
  7. Shepherd M. Interview on study329.org
  8. Sandler M. Interview on study329.org
  9. Ashcroft G. Interview on study329.org
  10. Axelrod J. Interview on study329.org
  11. Schildkraut JJ, interview on study329.org
  12. For more detail on this story see Healy, D. Let Them Eat Prozac (Toronto: Lorimer/ New York: New York University Press 2003).

Chapter 4

  1. Carlsson A, interview on study329.org
  2. Lambert P & CLRTP, interview on study329.org
  3. Pinder R, Interview on study329.org
  4. Rapoport J, Interview on study329.org
  5. Pedersen V & Bogeso K, interview on study329.org
  6. Coppen A, interview on study329.org
  7. Communication to Lilly U.S. from Lilly Bad Homburg by B v. Keitz, May 25, 1984, containing a translation of an unofficially received medical comment on the fluoxetine application to the German regulators.  This is on healyprozac.com
  8. Healy D, Let Them Eat Prozac, (New York University Press, New York 2004) p 36.
  9. Bech P, interview on study329.org
  10. Medawar C, interview on study329.org; Medawar C, The antidepressant web, International Journal of Risk & Safety in Medicine (1997) 10:75–125.
  11. Rosenbaum JF, Fava M, Hoog SL, Ashcroft RC, Krebs W, Selective serotonin reuptake inhibitor discontinuation syndrome: a randomised clinical study, Biological Psychiatry (1998), 44:77–87. See also socialaudit.org.uk

Chapter 5

  1. Shepherd M, interview on study329.org
  2. Carlsson A, interview on study329.org
  3. Healy D, Savage M, Reserpine exhumed, British Journal of Psychiatry (1998), 172(5):376–378
  4. Healy D, Mangin D, Does my Bias look Big in This? In Baylis F, Ballantyne, A. eds., Clinical Research involving Pregnant Women (Basal, Switzerland: Springer 2016), 197-208.
  5. Healy D, Le Noury J, Harris M, Butt M, Linden S, Whitaker C, Zou L, Roberts AP, Mortality for schizophrenia and related psychoses: data from two cohorts, 1875–1924 and 1994–2010, BMJ Open (2012), 2:e001810, doi:10.1136/bmjopen-2012-001810
  6. Cole J, Interview on study329.org
  7. King A, Riddle MA, Chappell PB, Hardin MT, Anderson GM, Lombroso P, Scahill L, Emergence of self-destructive phenomena in children and adolescents during fluoxetine treatment, Journal of American Academy of Child & Adolescent Psychiatry (1991), 30:171-176
  8. References to all these documents are available on study329.org in the SSRI Timeline as well as on healyprozac.com and in Healy, Let them Eat Prozac.
  9. Beasley CM, Dornseif BE, Bosomworth JC, Sayler ME, Rampey AH, Heiligenstein JH, Thomson VL, Murphy DJ, Masica DN, Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression, British Medical Journal (1991), 303:685–692.
  10. Deposition of Wilma Harrison in Miller Vs Pfizer, March 14, 2000.
  11. Fergusson D, Doucette S, Cranley-Glass K, Shapiro S, Healy D, Hebert P, Hutton B, The association between suicide attempts and selective serotonin reuptake inhibitors: systematic review of randomised controlled trials, British Medical Journal (2005), 330(7488):396–399,
  12. Healy, Let Them Eat Prozac.
  13. Trial testimony from Nancy Lord in Fentress vs Eli Lilly (October 24, 1994).
  14. Ibid., p. 49.
  15. Ibid., p. 54.
  16. Ibid., p. 52.
  17. Schulz-Solce N. Trial testimony in Fentress vs Eli Lilly by video from deposition, p. 185. See also chapter 11 for relevant figures on suicidal acts.
  18. In Cornwell J, The Power to Harm: Mind, Medicine, and Murder on Trial (New York: Viking, 1996), p. 286.
  19. Ibid., pp. 286–287.
  20. For more detail see Healy D, Herxheimer A, Menkes D, Antidepressants and violence: problems at the interface of medicine and law, PLoS Medicine (2006), 3, doi:10.1371/journal.pmed.0030372

Chapter 6

  1. Medicines and Healthcare Products Regulatory Agency. It is Britain’s equivalent of the FDA.
  2. For the following quotes see SSRI Timeline, study329.org
  3. Kuhn R, interview on study329.org
  4. Klein R, interview on study329.org
  5. BAP Meeting Transcript on study329.org
  6. Emslie GJ, Rush AJ, Weinberg WA, Kowatch RA, Hughes CW, Carmody T, Rintelmann J, A double-blind, randomized, placebo-controlled trial of fluoxetine in children and adolescents with depression, Archives of General Psychiatry (1997), 54:1031–1037.
  7. Healy, Let Them Eat Prozac.
  8. This letter and follow up correspondence are available on study329.org
  9. The video and transcript of this program are available on study329.org
  10. The video and transcript for “Emails from the Edge” are available on study329.org
  11. The description of this brochure are available in The Famous Grouse lecture on study329.org
  12. Available on study329.org
  13. Available on study329.org
  14. Lane C, Shyness (New Haven: Yale University Press, 2007).
  15. ACNP paper available on Timeline on study329.org
  16. The full document is on study329.org.
  17. A transcript of the hearings is available on study329.org
  18. Kondro, W. and Sibbald, B. Drug company experts advised staff to withhold data about SSRI use in children, CMAJ. Mar 2; 170 (5), (2004) 783. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC343848/
  19. Lancet Editorial, Depressing Research. Lancet 363, (2004), 1335.
  20. GlaxoSmithKline Settles Lawsuit with Spitzer, eCommerce Times, By Richard Casey, Aug 26, 2004
  21. A video and transcript of the program are available on study329.org
  22. A video and transcript of the program are available on study329.org

Chapter 7

  1. Emslie GJ, Rush AJ, Weinberg WA, Kowatch RA, Hughes CW, Carmody T, Rintelmann J, A Double-blind, Randomized, A placebo-Controlled Trial of Fluoxetine in Children and Adolescents With Depression, Archives of General Psychiatry (1997), 54:1031–37.
  2. Emslie GJ, Heiligenstein JH, Wagner KD, Hoog S, Ernest DE, Brown E, Nilsson M, Jacobson JG, Fluoxetine for acute treatment of depression in children and adolescents: a placebo-controlled, randomized clinical trial, Journal of the American Academy of Child & Adolescent Psychiatry (2002), 41:1205–1215.
  3. See Mosholder Medical Review of Prozac, 2001, on study329.org
  4. March SS, Petrycki S, Curry J, Wells K, Fairbank J, Burns B, Domino M, McNulty S, Vitiello B, Severe J, Treatment for Adolescents With Depression Study (TADS) Team, Fluoxetine, cognitive-behavioral therapy, and their combination for adolescents with depression: Treatment for Adolescents With Depression Study (TADS) randomized controlled trial, JAMA (2004), 292(7):807–820.
  5. Hogberg G, Antonnucio D, Healy D, Suicidal risk from TADS study was higher than it first appeared, International Journal of Risk & Safety in Medicine (2015), 27:85–91, doi:10.3233/JRS-150645
  6. Ibid
  7. To view letter go to link Background, timeline, 2002, Oct 10, at study329.org
  8. Transcript for this program is on study329.org
  9. Weller IVD, Ashby D, Brook R, Chambers MGA, Chick JD, Drummond C, Ebmeier KP, Gunnell DJ, Hawking H, Mukaetova-Ladinska E, O’Tierney E, Taylor RJ, York A, Zwi M, Report of the CSM Expert Working Group on the Safety of Selective Serotonin Reuptake Inhibitor Antidepressants (June 2003).
  10. To view Clinical Review document go to link Background, timeline,  February 1, 2004, at study329.org
  11. Kirsch I, The Emperor’s New Drugs (New York: Basic Books, 2010).
  12. Lenzer J, Drug Secrets: what the FDA isn’t telling. Slate Magazine (September 27 2005).
  13. A transcript of these two days hearings is on Study 329.org
  14. To view letter go to link Background, timeline, September 23, 2004 Statement of Robert Temple, M.D., Director, Office of Medical Policy, the FDA, at study329.org
  15. Program and transcript available on study329.org
  16. Report of the CSM Expert Working Group on the safety of selective serotonin reuptake inhibitors 2004. www.mhra.gov.uk/home/idcplg?IdcService= GET_FILE&dID=1391&noSaveAs=1&Rendition=WEB
  17. Report of the CSM Expert Working Group on the safety of selective serotonin reuptake inhibitors 2004. www.mhra.gov.uk/home/idcplg?IdcService= GET_FILE&dID=1391&noSaveAs=1&Rendition=WEB
  18. Healy D, Let Them Eat Prozac.
  19. Comment (October 1, 2008) by Lawrence Diller MD, Walnut Creek, CA, on Gibbons et al., SSRIs, adolescent suicide, and the Black Box: lingering questions, Psychiatric Times (October 1, 2007).
  20. American College of Neuropsychpharmacology, ACNP issues final report on SSRIs and suicidal behavior in youth: task force finds urgent need for effective treatment for depression in children and adolescents (November 23, 2005).
  21. Verkes RJ, Van der Mast RC, Hengeveld MW, Tuyl JP, Zwindermann AH, Van Kempen GM, Reduction by paroxetine of suicidal behavior in patients with repeated suicide attempts but not major depression, American Journal of Psychiatry (1998), 155:543–547.
  22. Update April 5th 2006, Paroxetine Adult Suicidality Analysis. gsk.com/media/paroxetine/briefing_doc.pdf
  23. GSK 2006 Press Release.
  24. To view the GSK Dear Health Care Professional letter go to link at study329.org, Background, timeline, see link at May, 2006
  25. U.S. Department of Health and Human Services, Food and Drug Administration (FDA) Centre for Drug Evaluation Research (CDER) Psychopharmacologic Drugs Advisory Committee (December 13, 2006). To view transcript go to link Background, Timeline, Dec 2006, at study329.org
  26. U.S. Food and Drug Administration, Antidepressant Use in Children, Adolescents, and Adults (May 2, 2007), www.fda.gov/Drugs/DrugSafety/InformationbyDrugClass/UCM096273
  27. Gibbons R, Brown CH, Hur K, Davis J, Mann JJ, Suicidal thoughts and behavior with antidepressant treatment: reanalysis of the randomized placebo-controlled studies of fluoxetine and venlafaxine, Archives of General Psychiatry (2012), 69(6):580–587, doi:10.1001/archgenpsychiatry.2011.2048;
  28. Gibbons RD, Hur K, Brown CH, Davis JM, Mann J, Benefits from antidepressants: synthesis of 6-week patient-level outcomes from double-blind placebo-controlled randomized trials of fluoxetine and venlafaxine, Archives of General Psychiatry  (2012), 69(6):572–579, doi:10.1001/archgenpsychiatry.2011.2044
  29. 1boringoldman blog, April 14 and 15, 2012, 1boringoldman.com
  30. Lu CY, Zhang F, Lakoma MD, Madden JM, Rusinak D, Penfold RB, Simon G, Ahmedani BK, Clarke G, Hunkeler EM, Waitzfelder B, Owen-Smith A, Raebel MA, Rossom R, Coleman KJ, Copeland LA, Soumerai SB. Changes in antidepressant use by young people and suicidal behavior after FDA warnings and media coverage: quasi-experimental study.  BMJ 2014; 348: g3596 doi: 10.1136/bmj.g3596
  31. For Rapid Responses to Lu et al – see Study 329.org
  32. Fiddaman B, Kelly Posner Gerstenhaber — incredulous!, Fiddaman Blog (May 25, 2017), https://fiddaman.blogspot.co.uk/2017/05/kelly-posner-gerstenhaber-incredulous.html#.WYRiY4jyvIV

Chapter 8

  1. Note: references for most of the material and documents in this chapter are available at study329.org (see Background, Requests to retract original Study 329) and in Jureidini J, Paxil study 329: paroxetine vs imipramine vs placebo in adolescents, Healthy Skepticism (January 2010), www.healthyskepticism.org/global/news/int/hsin2010-01
  2. Weintrob A, Paroxetine in adolescent major depression, Journal of American Academy of Child and Adolescent Psychiatry (2002) 41(4): 363.
  3. Parsons M, Paroxetine in adolescent major depression, Journal of American Academy of Child and Adolescent Psychiatry (2002), 41(4): 364.
  4. Keller MB, Ryan ND, Wagner KD, Paroxetine in adolescent major depression (reply), Journal of the American Academy of Child & Adolescent Psychiatry (2002), 41(4):364.
  5. Correll CU, Pleak RR, Paroxetine in adolescent major depression (letter to editor), Journal of the American Academy of Child & Adolescent Psychiatry (2002), 41(11):1269.
  6. Keller MB, McCafferty JP, Paroxetine in adolescent major depression (reply), Journal of the American Academy of Child & Adolescent Psychiatry (2002), 41(11):1270.
  7. Silveira R, Jainer AK, Singh R, Paroxetine in adolescent major depression (letter to editor), Journal of the American Academy of Child & Adolescent Psychiatry (2002), 41(11):1270.
  8. Jureidini J, Tonkin A, Paroxetine in major depression (letter to editor), Journal of American Academy of Child and Adolescent Psychiatry, (2003), 42(5):514
  9. http://www.healthyskepticism.org/files/docs/gsk/paroxetine/study329/Dulcan.pdf
  10. Jureidini J, Tonkin A, Paroxetine in major depression (letter to editor), Journal of American Academy of Child and Adolescent Psychiatry, (2003), 42(5):514.
  11. Keller MB, Ryan ND, Strober M, Weller EB, McCafferty JP, Hagino OR, Birmaher B, Wagner KD, Paroxetine in major depression (reply), Journal of the American Academy of Child & Adolescent Psychiatry (2003), 42(5):514–-515.
  12. Keller M, Keller deposition, Beverly Smith vs. SmithKline Beecham (September 6, 2006), redacted version on study329.org
  13. Laden S, Laden deposition. Beverly Smith vs. SmithKline Beecham (March 15, 2007), redacted version on study329.org
  14. Scientific Therapeutics Information, Inc (STI) (2006) www.stimedinfo.com (see McHenry and Jureidini, 2008 below).
  15. McHenry LB, Jureidini J, Industry sponsored ghostwriting in clinical trial reporting: a case study, Accountability in Research (2008), 15:152–167.
  16. Keller MB, Ryan ND, Strober M, Klein RG, Kutcher SP, Birmaher B, Hagino OR, Koplewicz H, Carlson GA, Clarke GN, Emslie GJ, Feinberg D, Geller B, Kusumakar V, Papatheodorou G, Sack WH, Sweeney M, Wagner KD, Weller EB, Winters NC, Oakes R, McCafferty JP, Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial, Journal of the American Academy of Child & Adolescent Psychiatry (2001), 40(7):762–772.
  17. Newman M, The rules of retraction, BMJ (2010), 341:c6985.
  18. British Broadcasting Corporation (BBC) Secrets of the drug trials, Panorama (January 29, 2007). Full transcript of the Jofre-Dulcan interview available on study329.org.
  19. Jureidini J, McHenry LB, Mansfield PR, Clinical trials and drug promotion: selective reporting of Study 329, International Journal of Risk & Safety in Medicine (2008), 20:73–81, doi: 10.3233/JRS-2008-0426
  20. Pinder R, interview on study329.org
  21. Jureidini JN, Jureidini ES, 226 Papers/Letters that Cite Keller et al.’s Report of GlaxoSmithKline’s Study 329 of Antidepressants for Adolescents (February 2008), www.healthyskepticism.org/files/docs/gsk/paroxetine/study329/Keller01Citations_000.doc
  22. Jureidini J, McHenry L, Conflicted medical journals and the failure of trust. Accountability in Research (2011), 18(1):45-54. Doi:1080/08989621.2011.542683.
  23. See Requests to retract on www.study329.org
  24. See Hide-and-go-seek …, 1boringoldman blog (December 21, 2012), 1boringoldman.com/index.php/2012/12/21/hide-and-go-seek/

Chapter 9

  1. Vickery A, interview on study329.org
  2. Murgatroyd S, interview on study329.org
  3. Menzies KB, interview on study329.org
  4. For depositions see study329.org
  5. Nemeroff C, interview on study329.org
  6. Keller M, deposition and personal accounts on study329.org
  7. Schatzberg A, interview on study329.org
  8. Healy D, Let Them Eat Prozac
  9. Nemeroff CB, Owens MJ, Treatment of Mood Disorders, Nature Neuroscience (2002), 5:1068-1070, doi: 10.1038/nn943.
  10. Peterson M, Undisclosed financial ties prompt reproval of doctor, New York Times (August 3, 2003), www.nytimes.com/2003/08/03/us/undisclosed-financial-ties-prompt-reproval-of-doctor.html
  11. Carroll B, Rubin R, Editorial policies on financial disclosure. Nature Neuroscience (2003) 6:999-1001, with response by Nemeroff C, Schatzberg A.
  12. Nemeroff CB, Mayberg HS, Krahl SE, McNamara J, Frazer A, Henry TR, George MS, Charney DS, Brannan SK, VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms, Neuropsychopharmacology (2006), 31:1345–1355.
  13. Armstrong D, Medical reviews face criticism over lapses, Pittsburgh Post-Gazette (from  Wall Street Journal) (July 19, 2006), www.postgazette.com/pg/06200/706933-114.stm
  14. Carey B, Correcting the errors of disclosure, New York Times (July 25, 2006), www.nytimes.com/2006/07/25/health/25news.html
  15. Nemeroff CB, Mayberg HS, Krahl SE, McNamara J, Frazer A, Henry TR, George MS, Charney DS, Brannan SK, Corrigendum: VNS therapy in treatment-resistant depression: clinical evidence and putative neurobiological mechanisms, Neuropsychopharmacology (2006) 31:2329, doi:10.1038/sj.npp.1301190
  16. Belanoff JK, Rothschild AJ, Cassidy F, DeBattista C, Baulieu EE, Schold C, Schatzberg AF, An open label trial of C-1073 (mifepristone) for psychotic major depression, Biological Psychiatry (2002), 52:386–392.
  17. Stotts B, Gadfly or watchdog? Accuracy in Academia (July 15, 2008), http://www.academia.org/gadfly-or-watchdog/
  18. Barney Carroll catalogued the evolution of this in a series of Health Care Renewal Blog posts that can be accessed on study329.org
  19. Preemption’s requiem in the wake of WYETH V. LEVINE (November 2016), www.baumhedlundlaw.com/pharmaceutical-articles/preemptions-requiem-wake-wyeth-v-levine/
  20. http://articles.latimes.com/2008/oct/04/science/sci-doctors4#
  21. Gøtzsche P, interview on study329.org
  22. Doshi P, Dickersin K, Healy D, Vedula SS, Jefferson T (2013).  Restoring invisible and abandoned trials: a call for people to publish the findings.  BMJ 346: f2865 doi: 10.1136/bmj.f2865
  23. Experts propose restoring invisible and abandoned trials “to correct the scientific record,” Science Daily (June 14, 2013)

Chapter 10

  1. For the full correspondence between the RIAT team and BMJ during this submission process, along with the responses from the BMJ reviewers in their entirety, see study329.org
  2. Winter C, MedDRA in clinical trials—industry perspective, SFDA‐ICH MedDRA workshop, Beijing (May 13-14, 2011), anyflip.com/hxlp/pijg/basic www.meddra.org/ sites/default/files/page/documents_insert/christina_winter_2_ meddra_in_clinical_trials_industry_perspective.pdf
  3. Le Noury J, Nardo J, Jureidini J, Healy D, Raven M, Aba-Jaoude E, Tufanaru C, Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence, BMJ (2015), 351:h4320, doi:10 .113 6/bmj.h4320

Chapter 12

  1. See UNITED STATES ex rel. GREG THORPE, ET AL. [Consolidated] Plaintiffs, v. GLAXOSMITHKLINE PLC, and GLAXOSMITHKLINE LLC, Defendants, www.justice.gov/sites/default/files/opa/legacy/2012/07/02/us-complaint.pdf#page=11

Chapter 13

  1. Basken P, Landmark analysis of an infamous medical study points out the challenges of research oversight, Chronicle of Higher Education (September 17, 2015), www.chronicle.com/article/Landmark-Analysis-of-an/233179/
  2. Linden, D, Re: Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence (rapid response), BMJ (September 22, 2015), www.bmj.com/content/351/bmj.h4320/rr-9.
  3. For all the rapid responses post publication of “Restoring Study 329” see study329.org or  http://www.bmj.com/content/351/bmj.h4320/rapid-responses
  4. Longo DL, Drazen JM, Data sharing, New England Journal of Medicine (2016), 374:276–277, doi:10.1056/NEJMe1516564
  5. Keller MB, Birmaher B, Carlson GA, Clarke GN, Emslie GJ, Koplewicz H, Kutcher S, Ryan N, Sack WH, Strober M, Re: Restoring Study 329: efficacy and harms of paroxetine and imipramine in treatment of major depression in adolescence: Response from the authors of the original Study 329 (rapid response), BMJ (January 18, 2016), www.bmj.com/content/351/bmj.h4320/rr-27
  6. Doshi P, Jefferson T, Response to Keller et al. re: RIAT, BMJ (January 20, 2016), www.bmj.com/content/351/bmj.h4320/rr-28
  7. Jureidini JN, Healy D, Nardo M, Raven M, Abi-Jaoude E, Tufanaru C, Le Noury J, Re: Restoring Study 329: Response to Keller and selected colleagues, BMJ (February 3, 2016), www.bmj.com/content/351/bmj.h4320/rr-29

Chapter 14

  1. Le Noury J, Nardo J, Healy D, Jureidini J, Raven M, Tufanuru C, Abi-Jaoude E, Study 329: continuation phase, International Journal of Risk & Safety in Medicine (2016), 28:143–161.
  2. For full copies of the JAACAP reviewers responses see study329

Chapter 15

  1. Joint meeting of the CDER Psychopharmacologic Drugs Advisory Committee and the FDA Pediatric Advisory Committee, Bethesda, MD (September 13, 2004), p. 332.
  2. Ibid., p. 435
  3. Controversial FDA official Tom Laughren retires, BioSpace (December 7, 2012), www.biospace.com/News/controversial-fda-official-tom-laughren-retires/281586