Overdosed America (46 page)

xiii
nine studies showing just the opposite:
Gardiner Harris, “Expert Kept From Speaking At Antidepressant Hearing,” New Warnings Sought on Antidepressants,”
New York Times
, April 16, 2004.

xiii
outside experts agreed with its own:
Gardiner Harris, “Antidepressant Study Seen to Back Expert,”
New York Times
, August 20, 2004.

xiii
FDA belatedly mandated the highest level of caution:
Gardiner Harris, “FDA Toughens Warning on Antidepressant Drugs,”
New York Times
, October 16, 2004.

xvii
securities analysts were receiving bonuses:
Speech given by Lori Richard, director of the Office of Compliance Inspections and Examinations, U.S. Securities and Exchange Commission, to the Financial Women’s Association, May 8, 2002. Viewed at http://www.sec.gov/news/speech/spch559.htm. Accessed January 30, 2004.

xvii
three times the average:
Henry J. Kaiser Family Foundation, “Prescription Drug Trends: A Chartbook Update,” November 2001. Viewed at http://www.kff.org/rxdrugs/loader.cfm?url=/commonspot/security/getfile.cfm&PageID=1 4267. Accessed January 31, 2004.

xvii
increased by more than $1000:
Milt Freudenheim, “Workers Feel Pinch of Rising Health Costs,”
New York Times,
October 22, 2003.

xvii
$469 for the average American family:
Paul Krugman, “The Tax-Cut Con,”
New York Times,
September 14, 2003.

xvii
an additional $469 per year:
Freudenheim, op. cit.

xvii
half of all personal bankruptcies:
“Harper’s Index,”
Harper’s Magazine,
August 2002.

4
Celebrex:
L. S. Simon, A. L. Weaver, D. Y. Graham, et al., “Anti-Inflammatory and Upper Gastrointestinal Effects of Celecoxib in Rheumatoid Arthritis: A Randomized Controlled Trial.”
Journal of the American Medical Association
282:1921–1928, 1999.

4
Vioxx:
M. J. Langman, D. M. Jensen, D. J. Watson, et al., “Adverse Upper Gastrointestinal Effects of Rofecoxib Compared with NSAIDs,”
Journal of the American Medical Association
282:1929–1933, 1999.

5
accompanying editorial:
W. L. Peterson and B. Cryer B., “COX-1-Sparing NSAIDS: Is the Enthusiasm Justified?”
Journal of the American Medical Association
282:1961–1963, 1999.

5
two of the four drugs:
“Prescription Drug Expenditures in 2000: The Upward Trend Continues,” a report by the National Institute for Health Care Management Research and Educational Foundation, May 2001. Viewed at http://nihcm.org/spending2000.pdf. Accessed August 3, 2003.

7
doctor and patient working together:
H. Benson, M.D., and M. Stark,
Timeless Healing: The Power and Biology of Belief,
New York: Scribner, 1996, p. 32.

10
the four medications:
I started Sister Marguerite on an angiotensin-converting enzyme (ACE) inhibitor to decrease her chance of going into congestive heart failure again, but she couldn’t tolerate even a low dose because of her already low blood pressure.

13
“Pravastatin Therapy and the Risk of Stroke”:
H. D. White, R. J. Simes, N. E., et al., “Pravastatin Therapy and the Risk of Stroke,”
New England Journal of Medicine
343:317–326, 2000.

15
there would be about one less stroke:
There was also a benefit in reduction of the risk of recurrent heart disease in the patients being treated with Pravachol, but those results had been published two years earlier and were not news. The point of this paper was to inform doctors about the additional benefit of stroke reduction.

16
age at which most strokes:
R. D. Brown Jr., J. P. Whisnant, J. D. Sicks, et al., “Stroke Incidence, Prevalence, and Survival: Secular Trends in Rochester, Minnesota, Through 1989,”
Stroke
27(3):373–380, 1996.

16
three out of five stroke victims in the general population are women:
Ibid.

16
do not take aspirin routinely:
Lawrence Goldkind, M.D., “Medical Officer’s Gastroenterology Advisory Committee Briefing Document. Celebrex (celecoxib),” February 7, 2001. p. 51. Viewed at http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b1_05_gi.doc.P. 10. Accessed September 26, 2001.

16
her risk of stroke would have been increased:
To be fair, none of the individual factors associated with an increased risk of stroke in the people treated with Pravachol reached statistical significance, but had these characteristics been grouped together into a typical stroke patient, the increased risk of stroke associated with taking Pravachol might well have reached statistical significance. And we cannot be sure that the same pattern of increased risk of stroke in these groups would occur in people who had not had a heart attack.

17
simply eating fish once a week:
H. Iso, K. M. Rexrode, M. J. Stampfer, et al., “Intake of Fish and Omega-3 Fatty Acids and Risk of Stroke in Women,”
Journal of the American Medical Association
285:304–312, 2001.

17
Controlling high blood pressure:
S. E. Straus, S. R. Majumdar, F. A. McAlister, “New Evidence for Stroke Prevention: Scientific Review,”
Journal of the American Medical Association
288:1388–1395, 2002.

17
moderate exercise for less than two hours:
R. L. Sacco, R. Gan, B. Boden-Albala, et al., “Leisure-Time Physician Activity and Ischemic Stroke Risk: The Northern Manhattan Stroke Study,”
Stroke
29(2):380–387, 1998.

18
a study about stroke prevention:
L. Sacco, R. Benson, D. Kargman, et al., “High-Density Lipoprotein Cholesterol and Ischemic Stroke in the Elderly,”
Journal of the American Medical Association
285:2729–2735, 2001.

19
follow-up letter to the editor:
K. Sheikh, “High-Density Lipoprotein Cholesterol and Risk of Stroke [Letters],”
Journal of the American Medical Association
286:1573–1574, 2001.

20
Statins raise HDL-cholesterol:
P. R. Hebert, J. M. Gaziano, K. S. Chan, and C. H. Hennekens, “Cholesterol Lowering with Statin Drugs, Risk of Stroke, and Total Mortality: An Overview of Randomized Trials,”
Journal of the American Medical Association
278:313–321, 1997.

20
far more than enough to significantly raise the risk of stroke:
Statins raise HDL cholesterol an average of 7 percent, or 2.8 mg/dL, and lower total cholesterol by 22 percent, or 42 mg/dL.

20
used data from the same case-control study:
R. L. Sacco, R. Gan, B. Boden-Albala, et al., op. cit.

20
earlier NEJM article about Pravachol:
H. D. White, R. J. Simes, N. E. Anderson, et al., “Pravastatin Therapy and the Risk of Stroke,”
New England Journal of Medicine
343:317–326, 2000.

21
life expectancy of a black man in Harlem:
Michael Marmot, “Inequalities in Health [Editorial],”
New England Journal of Medicine
345:134–136, 2001.

21
Pfizer had a new “HDL elevator” drug:
Jami Rubin and Andrew Baum. “Our Survey of the Statin Market Projects Strong Growth: Morgan Stanley Dean Witter,”
U.S. Investment Perspectives,
March 16, 2001, pp. 65–66.

23
editorial about Celebrex and Vioxx:
W. L. Peterson and B. Cryer, COX-1-Sparing NSAIDS: Is the Enthusiasm Justified?”
Journal of the American Medical Association
282:1961–1963, 1999.

24
over $3 billion in sales:
The National Institute for Health Care Management Research and Educational Foundation, “Prescription Drug Expenditures in 2000,” op. cit.

24
one-third of all arthritis drug sales:
“Prescription Drug Expenditures in 2001: Another Year of Escalating Costs,” a report by the National Institute for Health Care Management Research and Educational Foundation.” Revised May 6, 2002. Viewed at http://nihcm.org/spending2001.pdf p.15. Accessed February 20, 2004.

25
“The Coxibs, Selective Inhibitors of Cyclooxygenase-2”:
G. A. FitzGerald and C. Patrono, “The Coxibs, Selective Inhibitors of Cyclooxygenase-2,”
New England Journal of Medicine
345:433–442, 2001.

26
prohibited by the
New England Journal of Medicine
:
M. Angel, R. D. Utiger, A. J. J. Wood, “Disclosure of Authors’ Conflicts of Interest: A Follow-Up,”
New England Journal of Medicine
342:586–587, 2000.

26
NEJM loosened its editorial policy:
J. M. Drazen and G. D. Curfman, “Financial Associations of Authors,”
New England Journal of Medicine
346:1901–1902, 2002.

27
results of the VIGOR study from the fall of 2000:
C. Bombardier, L. Laine, A. Reicin, et al., op. cit.

27
keep the results of their studies secret:
T. Bodenheimer, Uneasy Alliance: Clinical Investigators and the Pharmaceutical Industry,”
New England Journal of Medicine
342:1539–1544, 2000.

28
Arthritis Advisory Committee meeting of February 7–8:
FDA Arthritis Advisory Committee, “Briefing Information. Celebrex (celecoxib),” February 7, 2001. Viewed at http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b1.htm.Accessed September 16, 2001. FDA Arthritis Advisory Committee, “Briefing Information. Vioxx (rofecoxib),” February 8, 2001. Viewed at http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b2.htm.Accessed September 16, 2001.

28
consider the manufacturers’ request:
Carol Eustice, “FDA Advised on Celebrex and Vioxx,”
What You Need to Know About Arthritis.
Viewed at http://arthritis.about.com/cs/cox/a/celebvioxxlabel.htm.

29
results of the CLASS study:
Silverstein, Faich, Goldstein, et al., op. cit.

29
The accompanying editorial:
D. R. Lichenstein and M. M. Wolfe, “COX-2-Selective NSAIDs: New and Improved?”
Journal of the American Medical Association
284(10):1297–1299, 2000.

29
manufacturer’s original research plan:
Goldkind, op. cit.

30
“the sponsor’s presentations of 6-month data . . . are not statistically valid or supportable”:
Ibid.

30
FDA’s gastroenterology reviewer concluded:
The FDA’s gastroenerology reviewer commented: “There appears to be a higher risk of late CSUGIEs [clinically significant upper gastrointestinal events] with C [Celebrex] compared to
both
ibuprofen and diclofenac.” Ibid, p. 52

30
story that had been published in the
Washington Post
:
S. Okie, “Missing Data on Celebrex Full Study Altered Picture of Drug,”
Washington Post,
August 5, 2001, p. A11. Viewed at http://www.washingtonpost.com. Accessed October 24, 2001.

31
“The primary objective of this study:
Goldkind, op. cit., p. 70.

31
“be categorized and analyzed separately”:
Ibid., p. 80.

31
“major strength of the current study”:
Ibid., p. 8.

32
experienced 11 percent more serious complications:
Ibid., p. 63.

32
The letter cites repeated unsubstantiated marketing claims:
FDA warning letter, February 1, 2001. Viewed at http://www.fda.gov/cder/warn/2001/DD8432.pdf. Accessed February 25, 2004.

34
“cardiovascular thrombotic or embolic”:
Lawrence Goldkind, M.D., Medical Officer’s Advisory Committee GI Briefing Document. Review of Vioxx Gastrointestinal Outcomes, February 8, 2001. Viewed at http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b2_05_gi.doc P. 54. Accessed October 17, 2001.

34
27
more
serious cardiovascular complications:
Shari L. Targum, M.D., “Review of Cardiovascular Safety Data Base: Rofecoxib (Vioxx),” February 1, 2001, p. 17. Viewed at http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b2_06_cardio.pdf. Accessed October 17, 2001.

34
increased risk of heart attacks, strokes, and sudden death:
The NEJM review article did not include the cardiovascular complications of unstable angina, serious blood clots, or transient ischemic attacks that had been submitted by the manufacturer to the FDA. See Targum, op. cit., p. 18.

35
statistical significance of this finding (
p
=
.0016):
Qian, Li, “Statistical Reviewer Briefing Document for the Advisory Committee,” February 8, 2001. Viewed at http://www.fda.gov/ohrms/dockets/ac/01/briefing/3677b2_04_stats.doc p. 12. Accessed October 17, 2001.

35
one additional serious cardiovascular complication:
Targum, op. cit., p. 15.

35
1.9 times the risk,
p
=
.041:
Qian, op. cit., p. 13.

35
would be the
preferred
drug:
Targum, op. cit., p. 13

35
between 7 and 11 additional serious cardiovascular complications each year:
Ibid., p. 21. The VIGOR study included people who might have had fewer cardiovascular complications if they had been taking low-dose aspirin, which was not permitted by the study design. For people with a previous history of cardiovascular disease, it is not known whether taking low-dose aspirin along with Vioxx would counteract the increased cardiovascular risk of taking Vioxx instead of naproxen. Nonetheless, although the magnitude of the risk of taking Vioxx instead of naproxen for people with a history of cardiovascular disease was not included in the NEJM review article, it did recommend that such people take low-dose aspirin along with their Vioxx. See www.fda.gov/ohrms/dockets/ac/01/briefing/367762_06_cardio.pdf, pp. 20–21.