The mortality effect: Counting the dead in the cancer trial

Public Culture

Volumn 22, Issue 1, 2010, Pages 89-117

  Lochlann Jain, S ^a  

^a NONE

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77954884382     PISSN: 08992363     EISSN: 15278018     Source Type: Journal    
DOI: 10.1215/08992363-2009-017     Document Type: Article

References (83)

1. Patient Information Leaflet FINALver.1.0, TroVax Renal Immunotherapy Survival Trial TRIST™ (accessed August 12, 2007). My italics.
2. Action to Cure Kidney Cancer, www.ackc.org/trovax (accessed June 16, 2009).
3. Mary-Jo DelVecchio Good, "The Biotechnical Embrace," Culture, Medicine and Psychiatry 25 (2001): 395-410.
4. Ilana Löwy, Between Bench and Bedside: Science, Healing, and Interleukin-2 in a Cancer Ward (Cambridge, Mass.: Harvard University Press, 1996).
5. Helen Valier and Carsten Timmermans, "Clinical Trials and the Reorganization of Medical Research in Post-Second World War Britain," Medical History 52 (2008): 509.
6. Cancer trials have often "delivered at best marginal benefits" with controversial endpoints and success difficult to assess. "Nevertheless, such controversy did not undermine the progress of the clinical trial as an increasingly essential feature of clinical bio-medical research" (Valier and Timmermans, "Clinical Trials," 501-2). "One of the new technologies that changed the face of clinical research was the clinical trial. The meaning of clinical trials has changed significantly since the 1950s.. .. Arguably this is a consequence of repeated reports on hopes associated with new experimental treatments since the 1960s (especially for childhood cancers) and the rigorous promotion of the randomized controlled trial as the gold standard of modern clinical research" (509).
7. Mitchell Dowsett, "William L. McGuire Memorial Lecture: Biomarking the Estrogen Dependence of Breast Cancer" (lecture presented at the San Antonio Breast Cancer Symposium [SABCS], San Antonio, Tex., December 14, 2007). The SABCS is the main forum in which breast cancer study results and interim research findings are presented each year.
8. Cancer trials differ from most other disease and drug trials in that they are typically not outsourced, though they may take place at several medical centers
9. Lauren Berlant writes of obesity as a form of "slow death," by which she means "the physical wearing out of a population and the deterioration of people in that population that is very nearly a defining condition of their experience and historical existence" ("Slow Death," Critical Inquiry 33 [2007]: 756). Cancer, like obesity, may be thought of as a form of slow death in that it can be analyzed and understood as related to forms of violence distributed in arbitrary and not so arbitrary ways and as a by-product of systems that require consumers and exposures.
10. Affective economies and RCT-based medical practice furthermore provide a basis on which to think through the recursive phenomena of what medical historians refer to as the increasing alienation of medical care: the treatment of and by strangers. Good finds that most people in America die under the direction of a physician who has known them for less than thirty-six hours ("The Biotechnical Embrace," 408). RCTs provide one place to see further how strangers, now as numbers, provide the grist for calculations in ways that have created industries often quite separate from cancer survival and treatment.
11. Only recently have patient advocacy groups been allowed at oncology conferences, and their admission is strictly regulated; it certainly is not genuinely participatory. At the SABCS meetings every December, for example, patient advocates each evening may listen to a panel of medical experts who translate the events of the day into lay language. The week I attended, the tone was sometimes condescending and sometimes simply explanatory, but the forum was never taken as an open exchange among knowledgeable participants in the cancer complex.
12. For a history of how groups came to be included in trials through the 1980s and 1990s in problematic ways that correlated along the lines of identity politics, see Steven Epstein, Inclusion: The Politics of Difference in Medical Research (Chicago: University of Chicago Press, 2007).
13. On the history of placebo trials, cytotoxic drugs, National Cancer Institute research, and oversight by the Food and Drug Administration (FDA), see David Rothman and Harold Edgar, "Scientific Rigor and Medical Realities: Placebo Trials in Cancer and AIDS Research," in AIDS: The Making of a Chronic Disease, ed. Elizabeth Fee and Daniel M. Fox (Berkeley: University of California Press, 1992), 194-207.
14. As Ann Oakley points out, they purposely elide humans, both patients and doctors, by not allowing either to decide which treatment arm the subject will belong to, treatment or placebo ("Who's Afraid of the Randomised Controlled Trial? Some Dilemmas of the Scientific Method and 'Good' Research Practice," in The Ann Oakley Reader: Gender, Women, and Social Science, ed. Ann Oakley [Bristol, U.K.: Policy, 2005], 233-44). In this sense, the RCT dispensed with several key questions in human subjects research, such as who should receive new treatments (the doctor's friends) and where pools of human subjects should be drawn from (prisoners, cancer patients).
15. Ted Porter, Trust in Numbers: The Pursuit of Objectivity (Princeton, N.J.: Princeton University Press, 1995).
16. Harry M. Marks, The Progress of Experiment: Science and Therapeutic Reform in the United States, 1900-1990 (Cambridge: Cambridge University Press, 1997).
17. Trudy DeHue, "Testing Treatments, Managing Life: On the History of Randomized Clinical Trials," History of the Human Sciences 12 (1999): 115-24
18. DeHue, "A Dutch Treat: Randomized Controlled Experimentation and the Case of Heroin-Maintenance in the Netherlands," History of the Human Sciences 15 (2002): 75-98
19. See, e.g., Vinceanne Adams, "Randomized Controlled Crime: Postcolonial Sciences in Alternative Medicine Research," Social Studies of Science 32 (2002): 659-90.
20. Adriana Petryna, When Experiments Travel: Clinical Trials and the Global Search for Human Subjects (Princeton, N.J.: Princeton University Press, 2009).
21. Joseph Dumit, "Drugs for Life" (unpublished manuscript)
22. Jill A. Fisher, Medical Research for Hire: The Political Economy of Pharmaceutical Clinical Trials (New Brunswick, N.J.: Rutgers University Press, 2009).
23. Fisher has found that the fact that 75 percent of trials are run privately by for-profit pharmaceutical companies fundamentally influences medical research. A legal perspective on costs of human experimentation and ways of dividing them by comparing car accidents and medical experiments appears in Guido Calabresi, "Reflections on Medical Experimentation in Humans," Daedalus 98 (1969): 387-405.
24. For the bioethics angle, see, e.g., Andrew Feenberg, "On Being a Human Subject: Interest and Obligation in the Experimental Treatment of Incurable Disease," Philosophical Forum 23 (1992): 213-30.
25. For a more classically bioethical perspective, see George Weisz, ed., Social Science Perspectives on Medical Ethics (Dordrecht: Kluwer, 1990).
26. According to James Holland of New York City's Mount Sinai Hospital: "Can it be more ethical to deny the possible good effects to most, by avoiding all toxicity in order to do no harm to one? The unmitigated disease must be calculated as a toxic cost of cancer. Underdosing, in an attempt to avoid toxicity, is far more deadly" (quoted in Rothman and Edgar, "Scientific Rigor and Medical Realities," 196).
27. Barron H. Lerner, The Breast Cancer Wars: Hope, Fear, and the Pursuit of a Cure in Twentieth-Century America (Oxford: Oxford University Press, 2001).
28. Eileen Welsome, The Plutonium Files (New York: Dial, 1999)
29. Gerald Kutcher, "Cancer Therapy and Military Cold War Research: Crossing Epistemological and Ethical Boundaries," History Workshop Journal 56 (2003): 105-30
30. Elizabeth Toon, Breast Cancer Therapy and Experience in Postwar Britain (New York: Palgrave Macmillan, 2009). The politics of cancer treatments happens in reverse as well; that is, as opposed to the adoption of treatments that increase survival only marginally, preventative measures can take a long time to be adopted. As Devra Davis shows, the broad adoption of the Pap smear to determine cervical precancerous polyps was delayed for decades because of professional debates about who would administer the tests and, Davis suggests, because of the huge amounts of money surgeons made by removing uteruses (The Secret History of the War on Cancer [New York: Basic Books, 2007]).
31. For other explanations of the introduction of the Pap smear, see Kirsten E. Gardner, Early Detection: Women, Cancer, and Awareness Campaigns in the Twentieth-Century United States (Chapel Hill: University of North Carolina Press, 2006).
32. Adele Clarke and Monica Casper, "Making the Pap Smear into the 'Right Tool' for the Job: Cervical Cancer Screening in the USA," Social Studies of Science 28 (1998): 255-90
33. James S. Olson, Bathsheba's Breast: Women, Cancer, and History (Baltimore, Md.: Johns Hopkins University Press, 2005), 84.
34. Oxford English Dictionary, 2nd ed. (1989), s.v. "guinea-pig," def. 1b.
35. Nicholas Christakis, Death Foretold (Chicago: University of Chicago Press, 2001), 11
36. This essay is based in part on my work with cancer survivors from 2005 to 2009. Unattributed quotations are drawn from this work.
37. James Paul, Rachael Seibl, and Todd Prescott found in 2004 that the cumulative number of clinical trials yielded 65,886 controlled trials, of which 32,760 were randomized control trials ("The Internet and Clinical Trials: Background, Online Resources, Examples, and Issues," www.ncbi.nlm .nih.gov/entrez/query.fcgi [accessed August 16, 2004]).
38. Causing and treating cancer are billion-dollar industries; Barbara Ehrenreich suggests that treatment alone costs $12-16 billion annually in the United States ("Welcome to Cancerland: A Mammogram Leads to a Cult of Pink Kitsch," Harper's, November 2001, 51). I have heard it said that one leukemia patient puts $6 million into the economy. Given the breadth of this industry (treatments, support groups, awareness posters, marches, basic research, pharmaceutical research, marketing, etc.), it is virtually impossible to assess the costs.
39. Porter, Trust in Numbers
40. See, e.g., Charles Rosenberg, "The Tyranny of Diagnosis: Specific Entities and Individual Experience," Milbank Quarterly 80 (2002): 237-60.
41. Science and technology studies scholars have broached the question of responsibility by examining where explanations rest in cases of technological failure or disaster. I find increasingly that in oncology, explanations do not rest anywhere, which results in a shocking erasure of ques tions regarding issues such as early detection, misdiagnosis, and environmental causes of cancer, each of which is barely on the fringes of what counts as oncology in journals, at conferences, and in the clinic. Here I examine the possibility that these blind spots result from the hegemony of the method and the way that it structures its questions and assumptions as relentlessly future-oriented, diverting attention from the careful study and analysis of past failures, treatment injuries, and missed diagnoses.
42. These traits are expected of the diagnosed body, which in biomedicine will become at different points a work object, an object of curiosity, and a fleshy mound in need of infusion and alteration. This mound uneasily houses this thing - this data point - of "life," but it also provides the workaday object of medical providers who may see tens, or even hundreds, of such bodies in a day or week.
43. It is fascinating to note that this is in direct opposition to the "survivor" rhetoric, which fetishizes the role of individual agency, and I think that it is no accident that both of these versions of agency take place in the context of a natural and social history of confusion about the causes and mechanisms of cancer
44. Another version of this self-abnegating nobility has been reported in the Canadian press in reference to a baby who will be a heart donor after her death: "She will leave behind more than just a heart-broken father and mother. Her parents will be the heroes behind her tragic sacrifice" (Don Martin, "Comment: Finding Good from Tragedy," National Post, April 9, 2009).
45. Michel Foucault, "The Political Technology of Individuals," in Power, ed. James D. Faubion, vol. 3 of The Essential Works of Michel Foucault, 1954-1984 (New York: New Press, 1994), 405.
46. Stuart Murray cites this quotation in a brilliant and suggestive piece, "Thanatopolitics: On the Use of Death for Mobilizing Political Life" (paper presented at the annual meeting of the American Political Science Association, Washington, D.C., September 1, 2005).
47. It is easy enough to reiterate these elisions by skipping the grief and moving straight into an academic argument. Maybe it is unavoidable; maybe the elision is the requirement of the academic narrative form. No one who writes about cancer can really escape the ways that language overwrites the helplessness and pain of mortality. The interpellation of the huge cancer statistics in the justification of research about cancer is horrifying, as if the large stats somehow ennobled researchers, justifying the bigness and importance of their work.
48. The following is a classic explication of this trade-off: "Society, having seen progress, asks not only for good care today, but for better care tomorrow and the medical profession has accepted this melioristic goal as legitimate and even obligatory. This has led to profound changes in a profession whose traditional commitment is to the individual patient. In order to give society the progress it demands for the future, we carry out clinical trials in which our patients of today become research subjects" (William J. MacKillop and Pauline A. Johnston, "Ethical Problems in Clinical Research: The Need for Empirical Studies of the Clinical Trials Process," Journal of Chronic Diseases 39, no. 3 [1986]: 178).
49. Margaret Edson, Wit (New York: Sagebrush Education Resources, 1999)
50. There are two ways of reading this aggregation. First, as I have argued elsewhere, the social logic of this leads to a way in which we come to live in populations and risk groups (S. Lochlann Jain, "Living in Prognosis," Representations 98 [2006]: 77-92). Second, actual clinical use in which an oncologist does his or her best to adjust a treatment to a patient is sometimes based on a trial's incredibly general terms, in which age, stage, and subtypes of cancer are not specific enough to draw conclusions from.
51. The vast numbers involved in the trials, the toxicity of the treatments for patients, the profits of drugs under patent for providers, and the incremental survival benefits consolidate cancer as a disease with a specific set of insights in relation to RCTs. This is different, say, from azidothymidine, or AZT, a drug that was designed two decades before the AIDS epidemic and that had no disease to work against until then. The efficacy of a drug so soon after the rise of the disease it is used to treat colors the cultural formations related to AIDS activism in ways that are insufficiently acknowledged in comparisons between AIDS and cancer activism. See Steven Epstein's rigorous account of AIDS activism's democratizing and lasting effect on RCTs in Impure Science: AIDS, Activism, and the Politics of Knowledge (Berkeley: University of California Press, 1996). I would argue that Epstein does not sufficiently recognize the efficacy of the medication in relation to the forms of and potential for activism.
52. See Steven Epstein's rigorous account of AIDS activism's democratizing and lasting effect on RCTs in Impure Science: AIDS, Activism, and the Politics of Knowledge (Berkeley: University of California Press, 1996). I would argue that Epstein does not sufficiently recognize the efficacy of the medication in relation to the forms of and potential for activism.
53. Elaine Scarry, The Body in Pain (New York: Oxford University Press, 1985), 119
54. Quoted in "Barbara Brenner's Reflections on the 30th Annual San Antonio Breast Cancer Symposium - Day 2," www.bcaction.org/index.php?page=2007-sabcs-day-2 (accessed March 6, 2008).
55. Elias Canetti writes that the commander of an army can appropriate all the dead bodies that result from his decision: "He commands; he sends his men against the enemy, and to their death. If he is victorious, all the dead on the battlefield belong to him, both those who fought for him and those who fought against him.. .. The significance of his victories is measured by the number of the dead" (Crowds and Power, trans. Carol Stewart [New York: Farrar, Straus and Giroux, 1960], 230).
56. The dead come to belong to the person who counts; otherwise deaths are dispersed and inexplicable. Canetti also writes of the autocrat's power over life and death. The autocrat "needs executions from time to time and, the more his fears increase, the more he needs them. His most dependable, one might say, his truest, subjects are those he has sent to their deaths" (232).
57. See also Drew Gilpin Faust's analysis of how the deaths related to the Civil War were understood: "The establishment of national and Confederate cemeteries created the Civil War Dead as a category, as a collective that represented something more and something different from the many thousands of individual deaths that it comprised. It also separated the Dead from the memories of living individuals mourning their own very particular losses.
58. The Civil War Dead became both powerful and immortal, no longer individual men but instead a force that would shape American public life for at least a century to come. The reburial movement created a constituency of the slain, insistent in both its existence and its silence, men whose very absence from American life made them a presence that could not be ignored" (This Republic of Suffering: Death and the American Civil War [New York: Vintage, 2008], 249).
59. Anatole Broyard, "The Patient Examines the Doctor," in Intoxicated by My Illness, and Other Writings on Life and Death (New York: Clarkson Potter, 1992), 45
60. Cliché might be considered, along with diagnosis and value-laden terms such as patient, as the linguistic philosopher J. L. Austin might describe it, a perlocutionary act, bringing one - by the very act of declaration - into a new subject position, one requiring a different set of customs, laws, ethics, and regulations.
61. See Robert Bazell, HER2: The Making of Herceptin, a Revolutionary Treatment for Breast Cancer (New York: Random House, 1998)
62. This quotation is preceded by "His calm and imperturbability in the midst of putrefaction [are] characteristic of the hero. All the people in the world could lie rotting on top of him and he would still remain, also in the midst of universal corruption, upright and intent on his goal" (Canetti, Crowds and Power, 257).
63. One way to view this position is to juxtapose two noncontemporary articles, one by the journalist and researcher Rose Kushner and the other by the physician and historian Barron H. Lerner writing about her: Kushner, "Is Aggressive Adjuvant Chemotherapy the Halsted Radical of the '80s?" CA: A Cancer Journal for Clinicians 34, no. 6 (1984): 345-52, in which Kushner discusses the debates in oncology over the introduction of chemotherapy for breast cancer.
64. Lerner, "Ill Patient, Public Activist: Rose Kushner's Attack on Breast Cancer Chemotherapy," Bulletin of the History of Medicine 81 (2007): 224-40. Another way is to talk to people who discussed medical options with many physicians before deciding on a course of action and who later found that they had been dissuaded from what became the standard of care - some with regrets, some without.
65. This is in part because treatments such as radiation and the use of hormones increase survival rates significantly over chemotherapy alone
66. The Rose Kushner Archive, Schlesinger Library, Harvard University, has a collection of these news clippings. See also Gerald Kutcher, "Cancer Clinical Trials and the Transfer of Knowledge: Metrology, Contestation, and Local Practice," in Devices and Designs: Medical Technologies in Historical Perspective, ed. Carsten Timmermans and Julie Anderson (London: Palgrave, 2006), 212-29.
67. After a twenty-year follow-up study, some oncologists claim a marginal benefit of the CMF regime, while others claim that there was no survival benefit. Still others think that its success is contingent on the population of patients, depending on their pre- or postmenopausal status and on the kind and stage of cancer. "Statistics based on immature data are not necessarily significant," asserts Stuart G. Gilbert. "As an example, I cite the landmark 1976 report by Bonadonna and colleagues, which established adjuvant chemotherapy with cyclophosphamide, methotrexate, and fluorouracil (CMF) for node-positive breast cancer. They reported an extraordinary benefit in progression-free survival among postmenopausal patients at 27 months (P = 0.001). However, at 36 months, there was less benefit (P = 0.16), and at 20 years, there was no survival benefit from having received CMF" ("Trastuzumab in Breast Cancer," Journal of the American Medical Association 354 [2006]: 640).
68. Of course, what counts as "mature" data, when one is studying survival rates, remains an open question. Since the introduction of chemotherapy in 1976, there have been two critical breakthroughs, each contingent on the ability to distinguish the hormone status of breast cancer: the development of tamoxifen and then of aromatase inhibitors, typically prescribed for estrogen-positive cancers, and the development of trastuzumab for the use of HER2/neu-positive cancers. The success of these treatments resulted from Dennis Slamon's discovery of the HER2/neu gene in 1986. This distinction in populations, critical to treatment regimens, was unavailable to the doctors leading studies in the 1970s, but it was available after 1986. In addition, it is possible to classify tumors even after the completion of trials if the tumors are kept.
69. The standard treatment became FAC (or FEC, depending on which anthracycline was used): fluorouracil, one of the anthracyclines, cyclophosphamide
70. The indication is for HER2/neu-positive and topo-IIa-coamplified tumors; in 2008 the FDA approved a test for detecting the topo IIa amplification
71. Dennis Slamon et al., "Role of Anthracycline-Based Therapy in the Adjuvant Treatment of Breast Cancer: Efficacy Analyses Determined by Molecular Subtypes of the Disease" (paper presented at the SABCS, San Antonio, Tex., December 13, 2007).
72. The distinctions in breast cancer trials make the results difficult to evaluate, because studies often combine stage I, II, and III diseases as well as women of different ages, in particular pre- and postmenopausal women
73. Rosenberg, "Tyranny of Diagnosis," 240
74. Discussing how physicians approach diagnosis, T. M. Luhrmann writes: "As they memorize the hyperdetails of bodily process, they. .. turn the emotional horror of disease into a scientific entity. That transformation leaves the person and the pain out of illness" (Of Two Minds: The Growing Disorder in American Psychiatry [New York: Knopf, 2000], 87).
75. Alternatively, a treatment that might have been highly successful for a few thousand people each year may have been abandoned because the market was not large enough
76. Mark N. Levine and Timothy Whelan, "Adjuvant Chemotherapy for Breast Cancer - Thirty Years Later," Journal of the American Medical Association 355 (2006): 1920-22.
77. Richard A. Rettig, Peter D. Jacobson, Cynthia M. Farquhar, and Wade M. Aubry, False Hope (New York: Oxford University Press, 2007).
78. For more examples of the extreme aggressiveness of cancer treatments, sometimes involving the surgical removal of body parts, see Lerner, Breast Cancer Wars
79. Many treatment-related injuries are not attributed to treatments for the primary disease; for instance, leukemia and heart failure are most often considered primary causes of death themselves, rather than results of treatments for the initial cancer
80. Scarry, Body in Pain, 80
81. The term out-healing was coined by Elaine Scarry in a discussion in which I was trying out the following argument with her (Stanford Humanities Center, Stanford, Calif., February 26, 2008).
82. In that sense, when Marks notes in passing that "I have yet to encounter a source that would tell me much about patients," he suggests that these accounts might somehow simply be added to the story of the rise of RCTs (Progress of Experiment, 13). The inclusion of patient narratives in his account might have required him to write an entirely different history of RCTs from the remarkable one he provides, because the patient does not deal in the immortal gathering of populations and chance.
83. As one therapist who works exclusively with people with cancer told me: "People get treated for years, and the doctors are excited [that] people are 'living' longer with cancer. So they live longer on endless cycles of chemo, feeling sick and being tied to the cancer centers for years. I think there is a sacrifice of human dignity and a giving up of knowing what it is like to die without the horrendous effects of chemo, being bald, sick, etc., etc. The huge attachment to these treatments also forces communities to sacrifice caring for their members who are dying. Instead these people are trying to live and survive cancer and [are] dying in the process" (Janie Brown, founder and therapist of Callanish, Vancouver, B.C., pers. comm., January 13, 2006).