Saturday, June 5, 2010

Tuskegee revisited

Pfizer, the global pharmaceutical giant, formally consumed the Wyeth pharma and consumer products company last year in a $68 billion merger. Thanks to a whistleblower lawsuit filed late last month, there could be hell to pay in addition to the billions Pfizer already shelled out for Wyeth.

A rogue and potentially dangerous off-label targeting of one of its drugs at African Americans has reawakened memories of one of medical science’s most pernicious experiments. Because of that, Pfizer may pay a price in public relations, if not actual dollars, for losing sight of what can happen when the company you keep becomes the company you acquire.

The Pharmalot blog, and more widely The Huffington Post, reported on May 25 that Marlene Sandler and Scott Paris, two former Wyeth hospital sales representatives, filed a lawsuit alleging Wyeth, years before Pfizer’s acquisition, illegally promoted the kidney transplant drug Rapamune to be used for other so-called off-label purposes, and targeted African-Americans — despite their being considered a high-risk patient group, according to the product’s own labeling and contraindication information. The suit was originally filed in 2005, but was recently unsealed and an amended complaint was refiled on May 24, Pharmalot reported.

From the Pharmalot story:
In arguing their case, the former reps contend Wyeth management “openly encouraged and directed their entire Rapamune sales force” to promote Rapamune to docs practicing heart, lung, liver, pancreas, and islet cell transplants even though the drug was never approved for patients receiving transplants of these organs, according to the suit. Reps, in fact, were provided off-label studies, abstracts and lists of studies to use when marketing Rapamune for off-label usage. And Wyeth allegedly offered doctors and hospitals kickbacks in the form of donations, grants and speaker fees to prescribe Rapamune off-label.

Rapamune is supposed to be administered following a kidney transplant and used in conjunction with cyclosporine and corticosteroids. However, cyclosporine is supposed to be withdrawn after two to four months, because it can eventually poison the kidneys, although this step is not approved for African-Americans and other high-risk groups. African-Americans are considered high-risk because they exhibit more vigorous immune responses to transplants. Wyeth managers were allegedly aware of limited data for Rapamune use in high-risk patients.

Despite limited data on high-risk patients, Wyeth targeted transplant centers that catered primarily to African-American patients, typically in urban areas. In 2005, Wyeth’s sales management selected Philadelphia’s Einstein Medical Center as a center on which to focus a Wyeth marketing plan designed to rapidly increase or accelerate Rapamune sales in a 90 day period. Einstein’s transplant patient population was approximately 75 percent African-American in 2005.
New York's SUNY Downstate Medical Center was also targeted, the suit alleges. Rapamune suppresses immune system response, preventing rejection of the new kidneys.

Marcus Baram of The Huffington Post reported that Rapamune generated $376 million in sales in 2008.

The amended suit claims: "As a result of Wyeth's wrongdoing, patients were put at risk of serious physical and financial harm, including: the disruption or discontinuation of stable treatment regimens; increased costs associated with treating side effects caused or exacerbated by Rapamune; life-threatening side effects such as anemia, bone marrow suppression, inhibited wound-healing, proteinuria, blood clots, leukopenia, thrombocytopenia, liver failure, pulmonary dehiscence; and death."



Among the lawsuit’s jaw-dropping allegations:
Wyeth Transplant Team management was aware that there was limited data for Rapamune use in high-risk patients and/or African-American patients. African-American transplant recipients are considered high-risk because they exhibit more vigorous immune responses to transplants than other patient groups. Some physicians in [whistleblower] Paris’ sales district, were concerned that the combination of Rapamune, cyclosporine and steroids lacked efficacy in African American or high risk patient groups and believed that that if higher levels of the approved combinations were used, serious side effects would result.

Wyeth’s 2002 Division Business Plan, “SWOT Analysis” (“Strengths, Weaknesses, Opportunities, and Threats”), lists as a Threat: “Limited data on use in high risk and special populations (African-American, Pediatric).

Despite limited data on high-risk patients, Wyeth targeted transplant centers that catered primarily to African-American patients, typically in urban areas. In 2005, Wyeth’s sales management (headed by National Director of Transplant Sales Joe McCafferty) selected Philadelphia’s Einstein Medical Center as a center on which to focus a Wyeth marketing plan designed to rapidly increase or accelerate Rapamune sales in a 90 day period. Einstein’s transplant patient population was approximately 75% African-American in 2005.

Wyeth management targeted SUNY Downstate Medical Center, whose patient population was in 2005 and still is predominantly African-American, for conversion protocols.

Wyeth’s business and marketing plans demonstrate that it continued to target transplant centers with significant African-American patient populations despite the dearth of data on this large patient pool.
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If you have the feeling we’ve been here before, it’s because, sadly, we have. The Wyeth experiment, its willful disregard of sound medical practice has its antecedent in the Tuskegee experiments conducted by the United States Public Health Service in Tuskegee, Ala. For 40 years, from 1932 to 1972, 399 black male sharecroppers were made the guinea pigs in a protracted medical charade, a series of trials in which African Americans were subjected to the most egregious vacancy of the spirit and practice of medical ethics since that of Nazi Germany.



In a nutshell, the Tuskegee syphilis experiments ring so loud and painfully for African Americans  because of their blatant validation of the suspicions black Americans have about medical science. The Tuskegee researchers deliberately let the disease run rampant through these 399 human beings for years, and then failed to treat patients even after penicillin, the first of the 20th-century’s wonder drugs, was proven to cure the disease, on a mass-marketed basis, during World War II.

As late as 1966, the federal Center for Disease Control upheld the study, saying it should run its course until all the people in the experiment had died and their bodies could be autopsied.

Even after the study was effectively shut down in July 1972 — after stories in the Washington Star and The New York Times — one Public Health Service doctor failed to grasp the human side of what he had done: "The men's status did not warrant ethical debate. They were subjects, not patients; clinical material, not sick people.”

According to Wikipedia, By 1972, “only 74 of the test subjects were alive. Twenty-eight of the original 399 men had died of syphilis, 100 were dead of related complications, 40 of their wives had been infected, and 19 of their children were born with congenital syphilis.”

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But the legacy of what’s been called "arguably the most infamous biomedical research study in U.S. history” may ironically have social dividends — and, for Wyeth’s new owner, consequences, too.

The undeniable social impact of the Tuskegee Syphilis Study ushered in as federal law such changes as patients’ informed consent — by which a patient has a hand in his or her own treatment by weighing of the facts as accurately presented by the doctor — and required accurate reporting of pertinent test results to the patient. It also led to federal laws requiring review boards to monitor the welfare of human subjects in clinical trials.

The outcome of the suit against Wyeth/Pfizer may well hinge on whether federal informed consent regulations were violated; whether Wyeth’s practice, motivated purely by a drive for sales, warrants any special punitive judgment; and, of course, whether or not anyone died.

Wyeth’s practice was a clinical trial, maybe not medically speaking but utterly “clinical” in another way, maybe the worst way — clinical as in indifferent, as in unfeeling. As in willfully ignorant of the human dimension of its actions.

A bow from the waist for Marlene Sandler and Scott Paris for standing up for that dimension.

Image credits: Wyeth, Pfizer logos, Rapamune logo: © 2010 Pfizer Inc. Fair use rationale is implicit in the newsworthiness of the subject of this content and its continuing importance to the American people. Undated Tuskegee blood draw image, Tuskegee study mortality table: Public domain. 

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