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FDA Warns Pfizer On Clinical Study Of Antipsychotic Geodo

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Pfizer not fixing test problems, FDA says

OPINION

JULY 10, 2009

Bookshelf

Helping Science, Making Money

Drug trials involving 20,000 people or more are now fairly common.

BY SCOTT GOTTLIEB

When I was a medical student, a pulmonary professor of mine cajoled me into joining a clinical trial that she was running. The general aim of the tests was to determine whether prolonged periods of short and shallow breathing would cause a person’s lungs to go into spasm. It turns out, as I can attest, that they do. After essentially panting for one hour, I became so acutely short of breath that I needed an albuterol inhaler to stop me from fainting. That was enough for me — I quit. But my professor called several times, pleading for me to reconsider. She didn’t want to lose me, she said, because I was a “perfect control subject.”

What she didn’t do was offer money as an enticement — a strategy that has become commonplace in recent years as clinical trials increasingly shift from academic settings and into the commercial realm, with companies recruiting and paying tens of thousands of people to participate in tests.

Clinical trials cover a broad range of medical matters, including the testing of new devices, theories (like prolonged shallow breathing leads to lung spasm) and approaches to care. But the most extensive clinical-trial testing is done on new drugs. That has always been the case, but nowadays meeting the ever more daunting requirements of the Food and Drug Administration has become such a logistical burden for pharmaceutical companies that they turn to businesses that specialize in administering clinical trials. These highly profitable companies, and the self-described human “guinea pigs” they hire, are the central focus of Alex O’Meara’s “Chasing Medical Miracles,” his investigation of “the promise and perils” of a $24 billion industry.

Mr. O’Meara himself has served as a clinical-trial guinea pig, and he writes with authority about the growing ranks of people who make something of a living from taking not-yet-FDA-approved drugs. If participants sign up for a long-term study, they’re said to be in “lockdown” until it’s over. Before they can take part in another clinical trial, the guinea pigs must observe a month-long “washout” period “to get all the drugs they ingested from the previous testing out of their systems.”

The author describes a world of clinical trials dominated by secretive companies, working on behalf of big drug makers, that are known (if at all) to trial participants by acronyms such as PPD (Pharmaceutical Product Development) and MDS Pharma Services (the company’s own Web site doesn’t say what the MDS stands for). The clinical-trial business itself is known by the acronym CRO, but Mr. O’Meara notes that even CRO doesn’t have a standard definition — some say it stands for “clinical research organizations” others say “contract research organizations” — which only adds to the industry’s reputation for stealthiness.

Mr. O’Meara worries about the portents of a large business sector’s maintaining such a low profile, but “Chasing Medical Miracles” is not so much an exposé as a worried portrait. The book is framed by the author’s account of his own guinea-pig experience. A lifelong diabetic with “brittle” disease, he has had to endure frequent finger pricks to obtain blood samples that can be checked for sugar levels. He enrolls in a clinical study that will try to stimulate the insulin-secreting activity of the pancreas by transplanting cells from cadaver pancreases.

His clinical-trial experience is the jumping off place for Mr. O’Meara — a freelance journalist who has worked for the Baltimore Sun and Newsday — to apply his reportorial skills to studying the CRO industry. He bunks with guinea pigs during lockdowns, talks to the heads of clinical-trial companies and meets the lawyers developing novel legal theories to sue them when something goes wrong, even though participants sign exhaustive waivers acknowledging the dangers inherent in testing new drugs and innovative medical procedures.

The guinea pigs that Mr. O’Meara trails are mostly in it for the money. Many are students or the marginally employed; not long ago, he says, the ranks of clinical-trial participants were often made up mostly of drying-out drunks and the homeless, but the burgeoning of the CRO business and the need for ever more patients has resulted in sweetened compensation. He’s sketchy on industry-wide rates, but does visit the sign-in for a clinical trail that pays participants $830 in exchange for a three-day confinement and two return visits.

Mr. O’Meara is adept at portraying clinical trials and in discussing ethical concerns — about CROs possibly skewing results to favor the interests of the drug companies that hire them, and about the financial incentive for clinical-trial applicants to lie about their medical history. But he gives too short shrift to the legal and regulatory forces that have prompted the rise of the CRO.

With the FDA increasingly concerned about ensuring drug safety, new layers of rules and requirements — including much wider and more extensive testing — have been added to an already complex approval system. A decade ago, a trial for a new blood-pressure pill might have enrolled a few thousand participants. Now late-stage trials on 20,000 people or more are fairly standard for these kinds of primary-care drugs. It is often simply beyond the capacity of an academic medical center or even a big pharmaceutical company to recruit and monitor the highly specific and often “treatment naïve” patients that the FDA typically requires.

As for the clinical-trial patient Alex O’Meara, the experimental cell-transplant diabetes treatment works for a time. He’s able to go off insulin and reduce the frequency of blood-sampling finger pricks. But eventually the transplanted cells start to fail. At the book’s close, he is clinically better off but not cured, satisfied just to have taken a shot — and content in the knowledge that he might have helped, in some small way, the advance of medicine.

Dr. Gottlieb, a practicing physician and resident fellow at the American Enterprise Institute, was a deputy commissioner of the Food and Drug Administration from 2005 to 2007. He is on the boards of two health-care companies that do business with CROs.

Copyright 2009 Dow Jones & Company, Inc. All Rights Reserved

• Zicam does not have FDA approval because it is a homeopathic remedy and not a “drug.” Like all such natural treatments including vitamins and other supplements, it is NOT REQUIRED to apply for or receive FDA approval for it to be marketed to the public.
• Because it has not undergone clinical trials for FDA approval, Zicam has no proven clinical benefits.
• In limited clinical trials., it has been shown that zinc, the active ingredient in Zicam, can shorten the severity and length of cold symptoms if treatment is received 24 hours after the onset of the cold.
• There is some discussion – chiefly in an article in today’s New York Times - that when zinc was tested as a nasal treatment for polio prevention in the 1930s it was found to cause anosmia. This is false. Clinical trials in the 1930s studying zinc sulfate – a different compound than the zinc gluconate in Zicam – revealed anecdotal evidence that some subjects suffered loss of smell.

A new piece of legislation in the U.S. House aims to increase clinical trials participation by allowing patients with rare diseases to become subjects in trials and not lose their government health insurance. The move is applauded by the Cystic Fibrosis Foundation as a new way to get medications from the research stage into the “hands of people who need them.” This is worth watching long term to see what the implications of this kind of fast-tracking is for drug development and for subjects and patients…. also, the FDA is putting tighter warnings on some asthma drugs because test facilities where some went through trials were not at all to up to par… All this plus industry news is in today’s update which you can read below…

New Legislation Seeks to Boost Participation in Clinical Trials … PR Newswire (press release) – New York, NY, USA – The “Improve Access to Clinical Trials Act” is co-sponsored by Representatives Edward J. Markey (D-MA) and Cliff Stearns (R-FL) and 30 members of the House … See all stories on this topic

FDA Move on Asthma Drug Warnings Comes After Complaints About … BNET – San Francisco, Ca, USA – The brazen “study buddy” and “crossover” arrangements, as staff referred to them, included churning or serially enrolling patients into clinical trials … See all stories on this topic

MarketWatch – USA – “In the past 30 months, we have conducted 14 clinical trials with the three product candidates that were licensed into Symphony Allegro…See all stories on this topic

Helix BioPharma Announces Q3 2009 Financial Results and Provides … MarketWatch –USA – The new expected timing of filing the confirmatory European Phase III Clinical Trial Application has not yet been established … See all stories on this topic

ERT to Showcase Its Clinical Trials Portfolio at DIA’s 45th Annual … MarketWatch – USA – The presentation entitled “Addressing Suicidality in Clinical Trials” will be chaired by John H. Greist, MD of HTS Inc and will discuss FDA safety concerns … See all stories on this topic

Clinical Trials Update: June 15, 2009 – U.S. News & World Report – Washington, DC, USA – If you are a current or former smoker, at least 40 years old, and have been diagnosed with COPD, you may qualify for this study. If you are age 16 or older … See all stories on this topic

Prostate Cancer Active Surveillance Protocol Clinical Trial … PR Web (press release) – Ferndale, WA, USA – NorthShore University HealthSystem (NorthShore) is conducting the only prostate cancer active surveillance clinical trial in the Chicago area and one of … See all stories on this topic

DZS Software Solutions to Preview clinplus® Clinical Trial … PR.com (press release) – Levittown, NY, USA – clinplus® expands their existing suite of clinical trial software and service solutions to include web-based Clinical Trial Management System (CTMS) … See all stories on this topic

EULAR: Good Efficacy Seen in RA for IL-6 Inhibitor – MedPage Today – Little Falls, NJ, USA – Explain that the drug is not FDA-approved and is currently available only in a clinical trial setting. Note that this study was published as an abstract and … See all stories on this topic

The letter puts the spotlight on how clinical trials are only as effective as the way in which the results are interpreted. In one case, results of clinical trials on computer-aided mammography devices showing they were ineffective were allegedly ignored by the FDA and the devices were repeatedly recommended for approval.

The FDA conducts on-site reviews of approximately one percent of all clinical trials. It’s not as simple as saying that the FDA is simply choosing to ignore results. That number is so low because of the staggering growth in the sheer volume and number of trials in an atmosphere of government deregulation in the last decade. The letter to Obama could be the first shot fired in a campaign to strengthen the FDA’s review processes of clinical trials. Such a campaign – while potentially painful for companies sponsoring clinical trials – could prove beneficial to trials subjects and to patients throughout the world.

(Read full story here.)