The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee

The Emperor of All Maladies: A Biography of Cancer by Siddhartha Mukherjee

Author:Siddhartha Mukherjee
Language: eng
Format: mobi, epub, azw3
Tags: Cancer - History, Oncology, Health & Fitness, Social Science, Cancer, Medical, Leukemia, Leukemia - history - United States, General, United States, Civilization, History, drug therapy, Antineoplastic Agents - history - United States, Biography & Autobiography, 20th Century - United States, Leukemia - History, Leukemia - drug therapy - United States, Diseases
ISBN: 9781439107959
Publisher: Simon and Schuster
Published: 2010-11-16T01:52:24.786000+00:00


Edinburgh was a disaster. Balkanized into hundreds of isolated and disconnected medical practices, it was a terrible trial site to begin with. Doctors assigned blocks of women to the screening or control groups based on seemingly arbitrary criteria. Or, worse still, women assigned themselves. Randomization protocols were disrupted. Women often switched between one group and the other as the trial proceeded, paralyzing and confounding any meaningful interpretation of the study as a whole.

The Canadian trial, meanwhile, epitomized precision and attention to detail. In the summer of 1980, a heavily publicized national campaign involving letters, advertisements, and personal phone calls was launched to recruit thirty-nine thousand women to fifteen accredited centers for screening mammography. When a woman presented herself at any such center, she was asked some preliminary questions by a receptionist, asked to fill out a questionnaire, then examined by a nurse or physician, after which her name was entered into an open ledger. The ledger—a blue-lined notebook was used in most clinics—circulated freely. Randomized assignment was thus achieved by alternating lines in that notebook. One woman was assigned to the screened group, the woman on the next line to the control group, the third line to the screened, the fourth to the control, and so forth.

Note carefully that sequence of events: a woman was typically randomized after her medical history and examination. That sequence was neither anticipated nor prescribed in the original protocol (detailed manuals of instruction had been sent to each center). But that minute change completely undid the trial. The allocations that emerged after those nurse interviews were no longer random. Women with abnormal breast or lymph node examinations were disproportionately assigned to the mammography group (seventeen to the mammography group; five to the control arm, at one site). So were women with prior histories of breast cancer. So, too, were women known to be at “high risk” based on their past history or prior insurance claims (eight to mammography; one to control).

The reasons for this skew are still unknown. Did the nurses allocate high-risk women to the mammography group to confirm a suspicious clinical examination—to obtain a second opinion, as it were, by X-ray? Was that subversion even conscious? Was it an unintended act of compassion, an attempt to help high-risk women by forcing them to have mammograms? Did high-risk women skip their turn in the waiting room to purposefully fall into the right line of the allocation book? Were they instructed to do so by the trial coordinators—by their examining doctors, the X-ray technicians, the receptionists?

Teams of epidemiologists, statisticians, radiologists, and at least one group of forensic experts have since pored over those scratchy notebooks to try to answer these questions and decipher what went wrong in the trial. “Suspicion, like beauty, lies in the eye of the beholder,” one of the trial’s chief investigators countered. But there was plenty to raise suspicion. The notebooks were pockmarked with clerical errors: names changed, identities reversed, lines whited out, names replaced or overwritten. Testimonies by on-site workers reinforced these observations.



Download



Copyright Disclaimer:
This site does not store any files on its server. We only index and link to content provided by other sites. Please contact the content providers to delete copyright contents if any and email us, we'll remove relevant links or contents immediately.