FDA Waved Through Asthma Drugs Despite Falsified Trials

by Martha Rosenberg
 
http://www.opednews.com/articles/FDA-Waved-Through-Asthma-D-by-Martha-Rosenberg-090527-1.html
 
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for suicidal side effects, were strengthened four times in 2007 and an antibiotic tested at Vivra, Raxar, was withdrawn altogether in 1999 after links to 13 deaths. Also tested at Vivra was norastemizole, a metabolite of Hismanal, an asthma drug withdrawn from the market in 1999 for cardiac-related 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 officia


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.
 
Martha Rosenberg is columnist and cartoonist based in Chicago In previous articles Dr. Michelle O'Donovan was wrongly identified as the Parexel employee (whose name is unknown) with whom Wayne MacFadden, the former US Medical Director for (more...)