How We Do Harm (40 page)

CHAPTER 2

My great-uncle Benjamin Brawley was a prolific writer.
My favorites among his more than a dozen books:
The Negro Genius
, first published in 1915 and last republished in 1966 by Biblo and Tannen.

Negro Builders and Heroes
, first published in 1937 by the University of North Carolina Press.

A Social History of the American Negro,
first published in 1923 and republished by Nabu Press in 2010.

Life expectancies of various countries come from
The World Factbook,
which is also known as the
CIA World Factbook
.
This reference resource is produced by the U.S.
Central Intelligence Agency with almanac-style information about the countries of the world.
It is available in book form and also as a Web site, which is updated regularly:
https://www.cia.gov/library/publications/the-world-factbook/
.

The Organisation for Economic Cooperation and Development (OECD) publishes data regarding more than fifty member nations.
It is the best source of health, economic, and outcomes data among countries:
http://www.oecd.org
.

CHAPTER 3

Much of my concern with American medicine focuses on the tendency of many physicians to make medical decisions without a good scientific basis: S.
Timmermans and A.
Mauck, “The promises and pitfalls of evidence-based medicine,”
Health Affairs (Millwood)
24, no.
1 (2005): 18–28; D.
M.
Eddy, “Evidence-based medicine: A unified approach,”
Health Affairs (Project Hope)
24, no.
1 (2005): 9–17, doi:10.1377/hlthaff.24.1.9.
PMID 15647211; and W.
A.
Rogers, “Evidence-based medicine and justice: A framework for looking at the impact of EBM upon vulnerable or disadvantaged groups,”
Journal of Medical Ethics
, 2004, retrieved December 7, 2007,
http://jme.bmj.com/cgi/content/full/30/2/141
.
Some medical research findings are influenced by the researchers having a financial interest in the findings.
In this study of the literature, more than one-third of research findings have at least one author with a conflict of interest: L.
S.
Friedman and E.
D.
Richter, “Relationship between conflicts of interest and research results,”
Journal of General Internal Medicine
19, no.
1 (January 2004): 51–56, doi:10.1111/j.1525-1497.2004.30617.x.
PMC 1494677.
PMID 14748860.
Having a conflict does not necessarily mean the researcher acted dishonestly.

The Halsted mastectomy was first performed by American surgeon William S.
Halsted of Johns Hopkins:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1272864/?page=1
.

Halsted first performed the radical mastectomy that now bears his name in the early 1890s.
He wrote about the procedure in this classic paper, whose title is ironic because he never did a rigorous formal outcomes assessment of the procedure: W.
S.
Halsted, “I.
The Results of Radical Operations for the Cure of Carcinoma of the Breast,”
Annals of Surgery
46 (1907): 1.

The modern surgical treatment of breast cancer was defined by Bernard Fisher, Umberto Veronesi, and colleagues through a number of well-designed clinical trials.
These physicians defined how clinical research should be done.
Classic papers were B.
Fisher, C.
Redmond, E.
R.
Fisher, et al., “Ten-year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation,”
New England Journal of Medicine
312, no.
11 (1985): 674; U.
Veronesi and P.
Valagussa, “Inefficacy of internal mammary nodes dissection in breast cancer surgery,”
Cancer
47 (1981): 170; U.
Veronesi, R.
Saccozzi, M.
Del Vecchio, et al., “Comparing radical mastectomy with quadrantectomy, axillary dissection, and radiotherapy in patients with small cancers of the breast,”
New England Journal of Medicine
305, no.
1 (July 2, 1981): 6–11; B.
Fisher, M.
Bauer, R.
Margolese, et al., “Five-year results of a randomized clinical trial comparing total mastectomy and segmental mastectomy with or without radiation in the treatment of breast cancer,”
New England Journal of Medicine
312, no.
11 (March 14, 1985): 665–73; B.
Fisher, S.
Anderson, C.
K.
Redmond, et al., “Reanalysis and results after 12 years of follow-up in a randomized clinical trial comparing total mastectomy with lumpectomy with or without irradiation in the treatment of breast cancer,”
New England Journal of Medicine
333 (1995): 1456; W.
A.
Maddox, J.
T.
Carpenter Jr., H.
L.
Laws,
et al.
“A randomized prospective trial of radical (Halsted) mastectomy versus modified radical mastectomy in 311 breast cancer patients,”
Annals of Surgery
198 (1983): 207; B.
Fisher, J.
H.
Jeong, S.
Anderson, et al., “Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation,”
New England Journal of Medicine
347 (2002): 567; and B.
Fisher, S.
Anderson, J.
Bryant, et al., “Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer,”
New England Journal of Medicine
347 (2002): 1233.

A wonderful overview of breast-conserving surgery (lumpectomy) and radiation is Early Breast Cancer Trialists’ Collaborative Group, “Effects of radiotherapy and surgery in early breast cancer.
An overview of the randomized trials,”
New England Journal of Medicine
333, no.
22 (1995): 1444.

The use of bone marrow transplant was invigorated when the following paper was published: W.
R.
Bezwoda, L.
Seymour, and R.
D.
Dansey, “High-dose chemotherapy with hematopoietic rescue as primary treatment for metastatic breast cancer: A randomized trial,”
Journal of Clinical Oncology
13 (1995): 2483–89.

The hope was dashed when it was revealed that other major trials did not demonstrate an advantage to the bone-marrow transplant and indeed showed a net harm.
Werner Bezwoda ultimately admitted that he had falsified most of the data in his trial: D.
Grady, “Breast cancer researcher admits falsifying data,”
New York Times,
February 5, 2000; M.
Hagmann, “Scientific misconduct.
Cancer researcher sacked for alleged fraud,”
Science
287, no.
5460 (March 17, 2000): 1901–2; Philadelphia Bone Marrow Transplant Group, “Conventional-dose chemotherapy compared with high-dose chemotherapy plus autologous hematopoietic stem-cell transplantation for metastatic breast cancer,”
New England Journal of Medicine
342, no.
15 (April 13, 2000): 1069–76; M.
S.
Tallman, R.
Gray, N.
J.
Robert, et al., “Conventional adjuvant chemotherapy with or without high-dose chemotherapy and autologous stem-cell transplantation in high-risk breast cancer,”
New England Journal of Medicine
349, no.
1 (July 3, 2003): 17–26; and K.
H.
Antman, “Overview of the six available randomized trials of high-dose chemotherapy with blood or marrow transplant in breast cancer,”
Journal of the National Cancer Institute
Monograph 2001 (30): 114–16.

CHAPTER 4

Long after I began thinking of the IHM nuns as feminists because they ran things, I discovered my idea was not original, as demonstrated in the title of this book on the history of the order:
Building Sisterhood: A Feminist History of the Sisters, Servants of the Immaculate Heart of Mary,
by Sisters, Servants of the Immaculate Heart of Mary in Books.

Much has been written about the Society of Jesus.
One of the books that I like is George W.
Traub, S.J.,
A Jesuit Education Reader
(Chicago: Loyola Press, 2008).

CHAPTER 6

An excellent overview of the history of overuse of red blood cell growth factors can be found in F.
R.
Khuri, “Weighing the hazards of erythropoiesis stimulation in patients with cancer,”
New England Journal of Medicine
356 (June 14, 2007): 2445–48.

An Amgen executive described his company’s products as “white juice” and “red juice” during a presentation at the Goldman Sachs 28
^th
Annual Global Healthcare Conference June 13, 2007.

German researcher Michael Henke discussed his surprising finding of harmful effects of erythropoietin in an interview with Paul Goldberg, “Study Tests a ‘Truth’ in Radiation Oncology, Raises Questions About Anemia Treatment,”
Cancer Letter,
October 24, 2003.

Henke published his results in M.
Henke, D.
Mattern, M.
Pepe, C.
Bézay, C.
Weissenberger, M.
Werner, and F.
Pajonk, “Erythropoietin receptors on cancer cells explain unexpected clinical findings?”
Journal of Clinical Oncology
24, no.
29 (October 10, 2006): 4708–13, doi: 10.1200/JCO.2006.06.2737Do.

Discussion of unexpected results of a randomized trial of erythropoietin in breast cancer is found in Brian Leyland-Jones, on behalf of the BEST Investigators and Study Group, “Breast cancer trial with erythropoietin terminated unexpectedly,”
Lancet Oncology
4, no.
8 (August 2003): 459–60.

Henke’s findings, BEST, and other studies cause many doctors to refrain from prescribing erythropoietin to patients with cancers of the breast and head and neck.
Discussion in Paul Goldberg, “FDA to Once Again Review ESA Label to Reflect Results of Negative Studies,”
Cancer Letter,
December 7, 2007.

The proper use of “white juice” is discussed in D.
C.
Dale, “Colony-stimulating factors for the management of neutropenia in cancer patients,”
Drugs
62, no.
S1 (2002): S1–S15.

In mid-2010, the ACS Cancer Action Network commissioned a survey of a nationally representative sample of the American population age eighteen and older who say they or a member of their household has cancer or a history of cancer:
http://www.acscan.org/healthcare/cancerpoll
.
The study found:
• High health costs jeopardize the ability of families affected by cancer to afford the care they need.

• High health costs also prevent people with cancer and their families from affording basic necessities.

• Affordability of care is a major issue for people under sixty-five.

• People with cancer and their families struggle to stay insured.

Early studies showed a benefit of 5-FU and leucovorin given adjuvantly after colon cancer surgery and removal of all known cancer for Stage III disease, and there was the suggestion of benefit for late Stage II (Stage bII) disease.

Clinical trials to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes’ B and C carcinoma of the colon: N.
Wolmark, H.
Rockette, E.
Mamounas, et al., “Results from National Surgical Adjuvant Breast and Bowel Project C-04,”
Journal of Clinical Oncology
17, no.
11 (1999): 3553.

Later studies showed a benefit to using oxaliplatin in the treatment of metastatic colon cancer and later as an adjuvant therapy in surgically resected Stage III colon cancer patients: T.
André, C.
Boni, L.
Mounedji-Boudiaf, et al., Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators, “Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer,”
New England Journal of Medicine
350, no.
23 (2004): 2343–47; and N.
Wolmark, S.
Wieand, P.
J.
Kuebler, et al., “A phase III trial comparing FULV to FULV + oxaliplatin in stage II or III carcinoma of the colon: Survival results of NSABP Protocol C-07,”
Journal of Clinical Oncology
26 (2008): 1008.

CHAPTER 7

The controversy concerning erythropoietin (EPO, Procrit, and Aranesp) is summarized in M.
R.
Savona and S.
M.
Silver,
“
Erythropoietin-stimulating agents in oncology,”
Cancer Journal
14, no.
2 (March–April 2008): 75–84.

Former pharmaceutical company attorneys who ran the FDA’s enforcement operations blocked efforts by agency staff to stop—or at least to tone down—the Procrit ads.
Internal FDA documents stemming from these unsuccessful efforts were obtained by the
Cancer Letter
and are covered in Paul Goldberg, “FDA Staff Efforts to Issue Warning Letters Were Stopped by FDA Counsel,” the
Cancer Letter
, May 9, 2008.

According to a January 24, 2011, report from Bloomberg, Amgen’s annual sales of Aranesp peaked at $4.1 billion in 2006 and have declined each year since after studies linked Amgen’s anemia drugs to increased risk of blood clots, heart attack, and stroke, as well as tumor growth in cancer patients.
Johnson & Johnson sales of erythropoietin peaked at $3.95 billion in 2003.

A twenty-eight-page summary of the reasons for higher-than-expected healthcare costs in the United States:
http://www.mckinsey.com/mgi/reports/pdfs/healthcare/US_healthcare_Executive_summary.pdf
.

CHAPTER 8

Implantable defibrillators were developed at the University of Maryland in Baltimore in the late 1970s and early 1980s: J.
A.
Kastor, “Michel Mirowski and the Automatic Implantable Defibrillator,”
American Journal of Cardiology
63 (1989): 977–82, 1121–26; and J.
A.
Kastor, A.
J.
Moss, M.
M.
Mower, and M.
L.
Weisfeldt, “Michel Mirowski: A Man with a Mission,”
PACE
14 (1991): 865.