Rigged Clinical Trials: Drug Studies Favor the Pharmaceutical Companies

[Magda Hassan]

Rigged Clinical Trials: Drug Studies Favor the Pharmaceutical Companies
Companies more concerned with profits than with patients


Global Research, November 7, 2008
Orthomolecular Medicine News Service - 2008-11-05


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If you have often suspected that drug studies are rigged by the pharmaceutical manufacturer, you are right. "Drug studies skewed toward study sponsors," reported The Washington Post. (1) "Industry-funded research often favors patent-holders, study finds." Specifically, the American Journal of Psychiatry study authors said, "In 90% of the studies, the reported overall outcome was in favor of the sponsor's drug... On the basis of these contrasting findings in head-to-head trials, it appears that whichever company sponsors the trial produces the better antipsychotic drug." (2)
Marcia Angell, MD, former editor-in-chief of the New England Journal of Medicine, agrees. "Is there some way (drug) companies can rig clinical trials to make their drugs look better than they are? Unfortunately, the answer is yes. Trials can be rigged in a dozen ways, and it happens all the time." One "way to load the dice," she writes, "is to enroll only young subjects in trials, even if the drugs being tested are meant to be used mainly in older people. Because young people generally experience fewer side effects, drugs will look safer." Another of the "common ways to bias trials is to present only part of the data - the part that makes the product look good - and ignore the rest." She adds, "The most dramatic form of bias is out-and-out suppression of negative results." (3)

You will rarely hear academia complain. Why? Because they are aboard the gravy train. Dr. Angell: "Columbia University, which patented the technology used in the manufacture of Epogen and Cerezyme, collected nearly $300 million in royalties" in 17 years. "The patent was based on NIH-funded research." That means you, the taxpayer, footed the bill. Harvard is in just as deep. In its own Faustian dealings with the drug companies, "a Harvard hospital has a deal that gives Novartis rights to discoveries that lead to new cancer drugs ... Merck is building a twelve-story research facility next door to Harvard Medical School . . . In Harvard Medical School 's Dean's Report for 2003-4, the list of benefactors included about a dozen of the largest drug companies."

Clearly drug companies are more concerned with profits than with patients. The psychiatric drug market is a very big business. American doctors prescribe $10 billion worth of antipsychotic drugs every single year. The pharmaceutical industry, says Angell, is "primarily a marketing machine to sell drugs of dubious benefit." Big pharma is "taking us for a ride." And it is no mere jaunt around the park. Total drug industry worldwide sales are in excess of $500 billion per year, half of which are in North America. Profit margins are typically 20 per cent, so high that "the combined profits for the ten drug companies in the Fortune 500 were more than the profits for all the other 490 businesses put together."

But more cash does not buy more cures. In fact, said the Washington Post: "When the federal government recently compared a broader range of drugs in typical schizophrenia patients in a lengthy trial, the two medications that stood out were cheaper drugs not under patent." (1) It gets even more interesting when we broaden our list of treatment options to include nutrition. With the therapeutic use of vitamin supplements, the cost goes down much further, and the success rate goes way up. Orthomolecular (nutritional) therapy, says psychiatrist Abram Hoffer, MD, PhD, is many times more effective than drug therapy. He says that niacin (vitamin B-3) in sufficiently high doses is the most effective, least expensive, and safest treatment for schizophrenia and a number of other very serious mental illnesses. Hoffer and colleagues demonstrated this decades ago when, in the early 1950s, they successfully conducted the very first double-blind, placebo-controlled nutritional studies in the history of psychiatry. (4)

Niacin is a clinically proven therapy for serious mental illness, and yet the medical profession has delayed endorsing it for over fifty years. Instead, drug treatments dominate. But drugs are not doing the job. A double-blind study of schizophrenics showed that three-quarters of them stopped taking pharmaceutical medication either because of intolerability or inefficacy. That means that either the drug side effects were unbearable, or the drug just plain did not work. (5)

Perhaps drugs are not the answer because mental illness is not caused by drug deficiency. But much illness, especially mental illness, may indeed be caused by nutrient deficiency or nutrient dependency. Only nutrients can correct this problem. This not only makes sense, it has stood up to clinical trial again and again. (6) Vitamins like niacin are cheap, safe and effective. Modern "wonder drugs" are none of those. But they do make money. Especially when the drug makers control the research, the advertising, and the doctors. No wonder which approach you've heard more about.

We've all been carefully taught that drugs cure illness, not vitamins. The system is remarkably well-entrenched. 2.3 million Americans per year serve as human subjects for pharmaceutical company drug testing. Pharmaceutical companies set up patient support or advocacy groups to attract specific subjects for their clinical trials. Doctors are paid an average of $7,000 per patient for every patient they enroll in a drug study. Drug companies pay nearly two-thirds of the costs of continuing medical education. While the pharmaceutical industry's reach into education is bad enough, its grip on research is scandalous. For example: Drug company "publications strategies" have them "sponsor minimal research, prepare journal articles based on it, and pay academic researchers to put their names on those articles." So bad is it that Dr. Angell wrote an editorial in NEJM (7) entitled "Is Academic Medicine for Sale?" A reader wryly responded, "No. The current owner is very happy with it."


The result? "Bias is now rampant in drug trials... (Pharmaceutical) industry-sponsored research was nearly four times as likely to be favorable to the company's product as NIH-sponsored research." (3) Remember, "NIH-sponsored" means "taxpayer-funded." And then, when they need to use a drug, those same taxpayers pay again, and way too much, for the drug they already paid out grant money to develop, in a rigged trial, for a high-profit company.

What a sweet system for the pharmaceutical industry.


NOTES

(1) Drug studies skewed toward study sponsors. Industry-funded research often favors patent-holders, study finds. Vedantam S. The Washington Post, April 11, 2006. http://www.msnbc.msn.com/id/12275329/from/RS.5/

(2) Heres S, Davis J , Maino K, et al. Why Olanzapine Beats Risperidone, Risperidone Beats Quetiapine, and Quetiapine Beats Olanzapine: An Exploratory Analysis of Head-to-Head Comparison Studies of Second-Generation Antipsychotics. Am J Psychiatry 163:185-194, February 2006. http://ajp.psychiatryonline.org/cgi/content/full/163/2/185

(3) Angell M. The Truth about the Drug Companies. NY: Random House, 2004.

(4) Hoffer A. Healing Schizophrenia. Complementary Vitamin & Drug Treatments. Ontario: CCNM Press (2004). ISBN-10: 1897025084; ISBN-13: 978-1897025086. Also: Vitamin B-3 and Schizophrenia: Discovery, Recovery, Controversy, by Abram Hoffer, MD. Quarry Press, Kingston, Ontario Canada (1998) ISBN 1-55082-079-6. Reviewed at http://www.doctoryourself.com/review_hoffer_B3.html

List of publications by Abram Hoffer: http://www.doctoryourself.com/biblio_hoffer.html

(5) Stroup TS, Lieberman JA, McEvoy JP et al. Effectiveness of olanzapine, quetiapine, risperidone, and ziprasidone in patients with chronic schizophrenia following discontinuation of a previous atypical antipsychotic. Am J Psychiatry. 2006 Apr;163(4):611-22. See also: Stroup TS, McEvoy JP, Swartz MS et al. The National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) project: schizophrenia trial design and protocol development. Schizophr Bull. 2003;29(1):15-31.

(6) For free access to peer-reviewed nutrition therapy journal articles: http://orthomolecular.org/library/jom

(7) Angell M. Is academic medicine for sale? N Engl J Med. 2000 May 18;342(20):1516-8.
Nutritional Medicine is Orthomolecular Medicine

Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information: http://www.orthomolecular.org

The peer-reviewed Orthomolecular Medicine News Service is a non-profit and non-commercial informational resource.

Editorial Review Board:
Damien Downing, M.D.
Steve Hickey, Ph.D.
Abram Hoffer, M.D., Ph.D.
James A. Jackson, PhD
Bo H. Jonsson, MD, Ph.D
Thomas Levy, M.D., J.D.
Erik Paterson, M.D.
Gert E. Shuitemaker, Ph.D.
Andrew W. Saul, Ph.D., Editor and contact person. Email: omns@orthomolecular.org
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http://globalresearch.ca/index.php?context=va&aid=10846

[Peter Lemkin]

All true. There is another interesting fact - that the Big Pharm companies, like the Big MIC Companies get grants [huge] and tax breaks and free use of Govt. Research Centers [CDC etc.]. The Capitalist Fat-Cats actually have a weird varient of 'socialism' only for themselves - they just don't want it for anyone else. Add to all this the out-of-control advertising/PR of drugs on TV, radio, print-media, via doctors [paid to promote certain drugs] under the last few administrations. Big anything in the Corporate world is now out of control - but in a Corporatocracy, who would expect otherwise.

[Magda Hassan]

Fraudulent Trials Behind Asthma Drugs Cited

Pay-to-Play Research Was Waved Through by FDA
by Martha Rosenberg / May 23rd, 2009
A major allergy and respiratory management company knowingly produced flawed clinical trials of FDA approved drugs currently on the market a Texas physician is charging.
Trials of Singular, Serevent, Foradil, Flovent, Xolair, Accolate and Xopenex conducted at the Tucson, AZ facility of Vivra Asthma & Allergy were corrupted by protocol violations and outright falsifications says Robert Davidson, MD, a former clinical research subinvestigator at the facility.
San Mateo, CA-based Vivra Asthma & Allergy was the nation’s largest respiratory disease physician practice until a merger with Lakewood, CO-based Gambro in 1997 and with El Segundo, CA-based DaVita in 2005.
In aggressive study subject recruitment schemes in the late 1990’s, patients with abnormal EKGs, multiple risk factors for coronary artery disease, arrhythmia, pulmonary embolism and rheumatic fever histories, acute illnesses and even pituitary tumors were enrolled with impunity in trials that earned investigators as much as $10,000 per patient charges Davidson. Patients were “prescreened” for asthma drug trials with medically unnecessary pulmonary function tests (PFTs) without their knowledge or consent and had medication dosages reduced in apparent efforts to qualify them for the lucrative trials.

Staff could be seen to enter rooms where placebo and real drugs were mixed, unblinding and invalidating entire studies sent to the FDA as data for new drug applications.
The brazen “study buddy” and “cross over” arrangements, as staff referred to them, included churning or serial enrolling of patients into clinical trials despite risks to their health and early terminations, coercing unwilling patients to participate and direct falsification of patient study diaries say documents filed by Davidson in a federal complaint.
In 2006, the FDA mandated black box warnings on Serevent and Foradil, tested at Vivra and elsewhere, for increasing the risk of asthma-related death after adverse outcomes forced the early termination of a large clinical trial. Warning labels for Singulair, also tested at Vivra and under FDA investigation for suicidal side effects, were strengthened four times in 2007 and an antibiotic tested at Vivra, Raxar, was withdrawn altogether in 1999 after links to 13 deaths.
FDA inspections of the Vivra Tucson facility where Jay Grossman, MD served as principal investigator (P.I.) from 1993-2000 confirm the clinical subterfuge.
“Three study coordinators stated that they saw diary card blank prior to subject entering exam room with P.I. for visit 2,” reads a report from a May 5 though June 28, 1999 inspection obtained under the Freedom of Information Act. “Five to ten minutes after, the diary had approximately two weeks of diary symptoms and peak flow entered.”
“On multiple occasions over the last 8 months the P.I. strongly counseled the S.I. [subinvestigator] to NOT mention potential risks of study participation to potential study subjects, (such as arrhythmia, drug-drug interaction, etc.) so as to not ’scare them away’,” the FDA report reads elsewhere.
“Coordinator stated that subject called to say she could not participate in a 12-hour a day study due to her schedule. P.I. called the subjects [sic] estranged husband to say that they had to get the disease under control.”
Nor was patient safety apparently protected.
“P.I. enrolled subject into study despite subject having a clear study exclusion (maintenance inhaled corticosteroid therapy),” an FDA report states elsewhere. “Subject subsequently experienced a SAE [severe adverse event] (hospitalized) while in the study. Moreover, this subject had recently participated in a prior study which she required multiple prednisone bursts and multiple courses of antibiotic therapy for several bouts of acute sinusitis with asthma exacerbation.”
FDA reports from a 1999 inspection at the Tucson Vivra facility also document missing informed consent forms, clinical records changed to minimize alcohol and cigarette consumption, and records rewritten and ripped up by Dr. Grossman according to witnesses.
Reached by telephone, communications officials at Gambro and DaVita were unable to discuss the trials. Dr. Grossman did not respond to faxed and email messages.
Questions have also been raised about the billing procedures of Vivra, which was acquired by Gambro in 1997. Pulmonary function tests were performed on all patients regardless of medical necessity states former Vivra Tucson nurse Joanne Wray in court documents–amounting to a time and money saving gratuity for drug companies, shouldered by insurers, to prevent costly “screening failures” when studies began.
In 2000, Gambro agreed to a $40 million settlement for submitting false claims to Medicare, Medicaid and TRICARE and entered into a Corporate Integrity Agreement with the Department of Health and Human Services only to have to agree to another settlement for $350 million in 2004.
Yet despite the irregularities and red flags, clinical trials at the Vivra Tucson facility which still appear in the New England Journal of Medicine and the Annals of Internal Medicine, were not stopped by the FDA, institutional review boards, trial sponsors, contract research organizations or the Justice Department. Nor was the facility’s clearance to conduct trials revoked.
In fact, FDA inspections were actually delayed to facilitate the new drug applications the studies were for–like clearing a plane with mechanical problems for takeoff to not hold up travelers. This “safety last” policy is a expected outgrowth of the 1992 Prescription Drug User Fee Act (PDUFA) that allows drug companies to pay the FDA to accelerate approvals, says Davidson.
“It takes time to obtain a properly administered, formal informed consent with full disclosure of risks and benefits and that slows study-subject recruitment and ultimately, delays the time to obtain market approval from FDA,” says Davidson. “It is virtually certain that there have been deaths of US citizens because of the fraudulent or seriously-flawed clinical research PDUFA encourages. Nor is FDA likely to revoke expedited market approvals because that would be tantamount to admitting that they ‘goofed.’”
When presented with 51 allegations of Vivra’s medical wrongdoing in 2000, the Arizona Board of Medical Examiners also did not act, calling the evidence “insufficient to support a violation” of Arizona Revised Statutes.
This is not the first time bogus, pay-to-play research which risks study subjects and the public’s health has surfaced. Recently Alabama physician Anne Kirkman Campbell began serving a sentence in a federal prison in Lexington, KY for clinical trials she conducted of the controversial, antibiotic Ketek, linked to liver failures and deaths.
Campbell “got greedy” and enrolled her own family, staff and more than one percent of the adult population of the town of Gadsden, AL in clinical trials wrote the St. Petersburg Times in 2007.
Despite revelations of Campbell’s fraud and problems found at other study sites by regulators while the drug was being tested, Ketek sailed through the FDA and was approved on April 1, 2004.
Ketek was also tested at the Tucson Vivra facility.
http://dissidentvoice.org/2009/05/fraudu...ugs-cited/