Bad Pharma: How Drug Companies Mislead Doctors and Harm Patients (52 page)

65
This was SmithKline Beecham, before they merged with GlaxoWellcome and became GSK.

66
Lenzer J, Brownlee S. Antidepressants: an untold story? BMJ 2008;336:532–4.

67
Wood AJ. Progress and deficiencies in the registration of clinical trials. N Engl J Med. 2009;360(8):824–830

68
O’Connor AB. The need for improved access to FDA reviews.
JAMA: The Journal of the American Medical Association
. 2009;302(2):191.

69
http://www.prescrire.org/editoriaux/EDI33693.pdf

70
Decision of the European Ombudsman closing his inquiry into complaint 2560/2007/BEH against the European Medicines Agency. November 2010. http://www.ombudsman.europa.eu/cases/decision.faces/en/5459/html.bookmark.

71
UK drug regulator destroys all the evidence after 15 years/BMI[Internet]. Available from http://www.bmj.com/rapid-response/2011/11/03/uk-drug-regulator-destroys-all-evidence-after-15-years.

72 You might be unsurprised to hear that no large drug company has ever been prosecuted under the safety monitoring regulations in the UK.

73
This story is spread over various publications by the Cochrane team, and the account here is taken from their work, published responses from Roche, and discussions with the Cochrane team. The best place to get the early half of this story is this paper: Doshi P. Neuraminidase inhibitors – the story behind the Cochrane review. BMJ. 2009;339. And for the second half, I recommend this open-access paper: Doshi P, Jefferson T, Del Mar C (2012) The Imperative to Share Clinical Study Reports: Recommendations from the Tamiflu Experience. PLoS Med 9(4): e1001201. doi:10.1371/journal.pmed.1001201 http://bit.ly/HIbwqO

74
This is a fascinating and messy new area. The paper below gives a good summary of the importance of analysing full trial programmes, and the discrepancies found on Tamiflu between papers and Clinical Study Reports: Jefferson T, Doshi P, Thompson M, Heneghan C, Group CARI. Ensuring safe and effective drugs: who can do what it takes? BMJ. 2011 Jan 11;342(jan11 1):c7258–c7258.

75
This is all from: Jefferson T, Doshi P, Thompson M, Heneghan C, Group CARI. Ensuring safe and effective drugs: who can do what it takes? BMJ. 2011 Jan 11;342(jan11 1):c7258–c7258.

76
Tom Jefferson, Lecture on Tamiflu, BMJ Evidence 2011, London.

77
Tramèr MR, Reynolds DJ, Moore RA, McQuay HJ. Impact of covert duplicate publication on meta-analysis: a case study. BMJ. 1997 Sep 13;315(7109):635–40.

78
Doshi P, Jefferson T, Del Mar C (2012) The Imperative to Share Clinical Study Reports: Recommendations from the Tamiflu Experience. PLoS Med 9(4): e1001201. doi:10.1371/journal. pmed.1001201 http://bit.ly/HIbwqO

79
Cohen D (2009) Complications: tracking down the data on oseltamivir. BMJ 339: b5387.

80
If you’re interested in this story, the links to primary documents are all here: Diabetes drug ‘victory’ is really an ugly story about incompetence. Ben Goldacre, The Guardian. 2010 Jul 17 [cited 2012 May 2]; Available from: http://www.badscience.net/2010/07/pharmaco-epidemiology-would-be-fascinating-enough-even-if-society-didnt-manage-it-really-really-badly/

81
Nissen SE. Setting the record straight. JAMA. 2010 Mar 24; 303(12):1194–5

82
Eichler H-G, Abadie E, Breckenridge A, Leufkens H, Rasi G. Open Clinical Trial Data for All? A View from Regulators. PLoS Med. 2012 Apr 10;9(4):e1001202.

83
This is a vast story, told well elsewhere. Start with Curfman GD, Morrissey S, Drazen JM. Expression of concern reaffirmed. N. Engl. J. Med. 2006 Mar 16;354(11):1193.

84
Opinion: Misleading Drug Trials. The Scientist [Internet]. [cited 2012 May 15]. Available from: http://thescientist.com/2012/05/14/opinion-misleading-drug-trials/

85
The Yale Open Data Archive project, or YODA, is one good example of how this might look in the future.

Chapter 2: Where do New Drugs Come From?

1
I recommend the classic medical student textbook ‘Rang and Dale’: Rang & Dale’s Pharmacology. 6th ed. Churchill Livingstone; 2007. But also this, on the regulatory process around early drug development: Friedhoff LT. New Drugs: An Insider’s Guide to the FDA’s New Drug Approval Process for Scientists, Investors and Patients. 1st ed. PSPG Publishing, 2009.

2
Elliott C, Abadie R. Exploiting a research underclass in phase 1 clinical trials. New England Journal of Medicine. 2008;358(22):2316.

3
Cohen LP. To screen new drugs for safety, Lilly pays homeless alcoholics: it’s ‘quick cash’ to habitues of Indianapolis shelters; it vanishes quickly, too. Wall St J (East Ed). 1996 Nov 14;A1, A10.

4
Abadie R. The Professional Guinea Pig: Big Pharma and the Risky World of Human Subjects. 1st ed. Duke University Press, 2010.

5
Helms R, editor. Guinea Pig Zero: An Anthology of the Journal for Human Research Subjects. 1st ed. Garrett County Press; 2006.

6
Tucker T. Great Starvation Experiment: Ancel Keys and the Men Who Starved for Science. 1st University of Minnesota Press Ed. University of Minnesota Press; 2008.

7
Gorkin L, Schron EB, Handshaw K, Shea S, Kinney MR, Branyon M, et al. Clinical trial enrollers vs. nonenrollers: The Cardiac Arrhythmia Suppression Trial (CAST) Recruitment and Enrollment Assessment in Clinical Trials (REACT) project. Controlled Clinical Trials. 1996 Feb;17(1):46–59.

8
Sheppard VB, Cox LS, Kanamori MJ, Cañar J, Rodríguez Y, Goodman M, et al. BRIEF REPORT: If You Build It, They Will Come. J Gen Intern Med. 2005 May;20(5):444–7.

9
ACRO – CRO Market [Internet]. [cited 2012 Feb 11]. Available from: http://www.acrohealth.org/cro-market1.html.

10
MacDonald T, Hawkey C, Ford I. Time to treat as independent. BMJ. 2010 Nov 30;341(nov30 2):c6837–c6837.

11
Kassirer J. On the Take: How Medicine’s Complicity with Big Business Can Endanger Your Health. Ch 8. 1st ed. Oxford University Press, USA; 2004.

12
Pharmaceutical CSO – Pharmaceutical Commercialization – Quintiles [Internet.] Available from: http://www.quintiles.com/commercial-services/

13
DRUG TESTING GOES OFFSHORE – August 8, 2005 [Internet]. [cited 2012 Feb 11]. Available from: http://money.cnn.com/magazines/fortune/fortune_archive/200 5/08/08/8267653/index.htm

14
Thiers FA, Sinskey AJ, Berndt ER. Trends in the globalization of clinical trials. Nature Reviews Drug Discovery. 2008 Jan;7(1):13–4.

15
All of the issues around trials in developing countries are well covered in two books, Shah S. BODY HUNTERS, THE: Testing New Drugs on the World’s Poorest Patients. SCIE. THE NEW PRESS; 2007. And Petryna A. When Experiments Travel: Clinical Trials and the Global Search for Human Subjects. 1st ed. Princeton University Press; 2009.

16
Ethical and Scientific Implications of the Globalization of Clinical Research Seth W. Glickman, M.D., M.B.A., John G. McHutchison, M.D., Eric D. Peterson, M.D., M.P.H., Charles B. Cairns, M.D., Robert A. Harrington, M.D., Robert M. Califf, M.D., and Kevin A. Schulman, M.D. N Engl J Med 2009; 360:816–823. February 19, 2009.

17
Bansal N. The opportunities and challenges in conducting clinical trials globally. Clinical Research and Regulatory Affairs. 2012 Feb 9;1–6.

18
Ethical and Scientific Implications of the Globalization of Clinical Research Seth W. Glickman, M.D., M.B.A., John G. McHutchison, M.D., Eric D. Peterson, M.D., M.P.H., Charles B. Cairns, M.D., Robert A. Harrington, M.D., Robert M. Califf, M.D., and Kevin A. Schulman, M.D. N Engl J Med 2009; 360:816–823. February 19, 2009

19
Hyder AA, Wali SA, Khan AN, Teoh NB, Kass NE, Dawson L. Ethical review of health research: a perspective from developing country researchers. J Med Ethics. 2004 Feb;30(1):68–72.

20
Zhang D, Yin P, Freemantle N, Jordan R, Zhong N, Cheng KK. An assessment of the quality of randomised controlled trials conducted in China. Trials. 2008;9:22.

21
FDA Requires Foreign Clinical Studies be in Accordance with Good Clinical Practice to Better Protect Human Subjects by W. Thomas Smith – American Bar Association Health eSource October 2008 Volume 5 Number 2 [Internet]. [cited 2012 Feb 11]. Available from: http://www.americanbar.org/newsletter/publications/aba_healt h_esource_home/Volume5_02_smith.html

22
WikiLeaks cables: Pfizer ‘used dirty tricks to avoid clinical trial payout’ – Business – The Guardian [Internet]. [cited 2012 Feb 11]. Available from: http://www.guardian.co.uk/business/2010/dec/09/wikileaks-cables-pfizer-nigeria

23
US embassy cable Monday 20 April 2009, 16:00, Abuja 000671 ‘Pfizer reaches preliminary agreement for $75m settlement’ [cited 2012 Feb 11]. Available from: http://www.guardian.co.uk/world/us-embassy-cables-documents/203205

24
WikiLeaks cables: Pfizer ‘used dirty tricks to avoid clinical trial payout’ – Business – The Guardian [Internet]. [cited 2012 Feb11]. Available from: http://www.guardian.co.uk/business/2010/dec/09/wikileaks-cables-pfizer-nigeria

25
Jonathan Kimmelman, Charles Weijer, and Eric M Meslin, ‘Helsinki discords: FDA, ethics, and international drug trials,’
The Lancet
373, no. 9657 (January 3, 2009): 13–14.

26
Goodyear MDE, Lemmens T, Sprumont D, Tangwa G. Does the FDA have the authority to trump the Declaration of Helsinki? BMJ. 2009 Apr 21;338(apr21 1):b1559–b1559.

Chapter 3: Bad Regulators

1
Royal College of Physicians, London UK. INNOVATING FOR HEALTH. Patients, physicians, the pharmaceutical industry and the NHS. February 2009. Report of a Working Party.

2
If you’re very confused about the European Medicines Agency, and the UK MHRA, and how they relate to each other, it’s fairly simple. The MHRA used to approve drugs, now the EMA do, but they farm out some of the local work to the old national regulators, especially monitoring and communication, as well as some of the approval stuff.

3
I recommend the work of John Abraham, collected here: http://www.sussex.ac.uk/profiles/6

4
Owen BM, Braeutigam R. The Regulation Game: Strategic Use of the Administrative Process. Ballinger Pub Co; 1978. Via Abraham J. On the prohibition of conflicts of interest in pharmaceutical regulation: Precautionary limits and permissive challenges. A commentary on Sismondo (66:9, 2008, 1909–14) and O’Donovan and Lexchin. Social Science & Medicine. 2010 Mar;70(5):648–51.

5
http://www.alter-eu.org/sites/default/files/documents/lonngrendoc.pdf

6
http://www.alter-eu.org/sites/default/files/documents/lonngrendoc.pdf

7
http://www.alter-eu.org/fr/press-releases/2011/02/25/conflict-of-interest-case-involving-ex-ema-director

8
http://www.corporateeurope.org/publications/block-revolving-door

9
Lurie, P., Almeida, C., Stine, N., Stine, A. R., & Wolfe, S. M. (2006). Financial conflict of interest disclosure and voting patterns at food and drug administration drug advisory committee meetings. JAMA, 295, 1921e1928.

10
If you’re interested in starting on this, the following are a good place to start: http://www.nytimes.com/2009/09/25/health/policy/25knee.html?_r=1; http://www.nytimes.com/2005/02/25/politics/25fda.html. And the work of the Project On Government Oversight is excellent, led by the researcher who worked on Senator Grassley’s reports into the pharmaceutical industry: http://www.pogo.org/investigations/public-health/fda.html; http://pogoblog.typepad.com/pogo/2011/08/fdas-janet-woodcock-the-substance-behind-her-nonsubstantive-substantive-ties-to-industry.html

11
Light D, editor. The Risks of Prescription Drugs (A Columbia/SSRC Book. Columbia University Press; 2010).

12
Survey of FDA Scientists Shows They Feel Pressure to Exclude…: Oncology Times [Internet]. [cited 2012 May 6]. Available from: http://journals.lww.com/oncologytimes/Fulltext/2006/08250/Survey_of_FDA_Scientists_Shows_T hey_Feel_Pressure.8.aspx

13
USATODAY.com – Survey: FDA scientists question safety [Internet]. [cited 2012 May 6]. Available from: http://www.usatoday.com/news/health/2004-12-16-fda-survey-usat_x.htm

14
European Journal of Clinical Pharmacology 2011 10.1007/s00228-011-1052-1 Anything new in EU pharmacovigilance? Silvio Garattini and Vittorio Bertele’.

15
Goldberg NH, Schneeweiss S, Kowal MK, Gagne JJ. Availability of Comparative Efficacy Data at the Time of Drug Approval in the United States. JAMA: The Journal of the American Medical Association. 2011 May 4;305(17):1786–9.

16
Bertele’ V, Banzi R, Gluud C, Garattini S. EMA’s reflection on placebo does not reflect patients’ interests. European Journal of Clinical Pharmacology [Internet]. 2011 Dec 2 [cited 2012 Feb 13]; Epub ahead of print. Available from: http://www.springerlink.com/content/4j733734v35381jk/

17
Garattini S, Chalmers I. Patients and the public deserve big changes in evaluation of drugs. BMJ. 2009 Mar 31;338(mar31 3):b1025–b1025.