1 Boring Old Man

The Internet is a really big place. Just searching with Google™ or one of its cousins doesn’t always get the job done, so one learns to find people who are ahead of the game. I want to look at how these Cinical Research Center Clinical Trials work, so I started looking at the blogs and I scored on my first waypoint, Soulful Sepulcher, Stephany’s blog. Somewhere down the page, I ran into a post about South Coast Clinical Trials , a Clinical Research Center in Anaheim CA that does rather remarkable videocasts posted on their web-site, The Clinical Trials Guru. The site puts a face on the Clinical Trial Center subjects. The video on the left talks about how to "find a study." The one on the right is an interview with a couple of subjects who know the ropes – Clinical Trials veterans so to speak:

Don Walters does the legwork involved in recruiting and Dan Sfera is the organizer and liason with the sponsors and CROs [bios]. You got to admire their candidness and the fact that they sort of act as advocates for their "database." Here’s Don talking about recruitment:

Nose around their videos, particularly the client interviews to get a feel for the people who become subjects in these trials. Don’t miss Dan’s rock-video introduction to his eBook, Demystifying Clinical Trials [the book itself is a fine introduction for people looking to become a Clinical Trials subject].

Deadly Medicine
Vanity Fair
by Donald E, Bartlett and James Steele
January 2011

^{Prescription drugs kill some 200,000 Americans every year. Will that number go up, now that most clinical trials are conducted overseas — on sick Russians, homeless Poles, and slum-dwelling Chinese — in places where regulation is virtually nonexistent, the F.D.A. doesn’t reach, and “mistakes” can end up in pauper’s graves? The authors investigate the globalization of the pharmaceutical industry, and the U.S. Government’s failure to rein in a lethal profit machine…}

^{Once upon a time, the drugs Americans took to treat chronic diseases, clear up infections, improve their state of mind, and enhance their sexual vitality were tested primarily either in the United States (the vast majority of cases) or in Europe. No longer. As recently as 1990, according to the inspector general of the Department of Health and Human Services, a mere 271 trials were being conducted in foreign countries of drugs intended for American use. By 2008, the number had risen to 6,485 — an increase of more than 2,000 percent. A database being compiled by the National Institutes of Health has identified 58,788 such trials in 173 countries outside the United States since 2000. In 2008 alone, according to the inspector general’s report, 80 percent of the applications submitted to the F.D.A. for new drugs contained data from foreign clinical trials. Increasingly, companies are doing 100 percent of their testing offshore. The inspector general found that the 20 largest US-based pharmaceutical companies now conducted “one-third of their clinical trials exclusively at foreign sites” …}

^{Many of today’s trials still take place in developed countries, such as Britain, Italy, and Japan. But thousands are taking place in countries with large concentrations of poor, often illiterate people, who in some cases sign consent forms with a thumbprint, or scratch an “X.” Bangladesh has been home to 76 clinical trials. There have been clinical trials in Malawi (61), the Russian Federation (1,513), Romania (876), Thailand (786), Ukraine (589), Kazakhstan (15), Peru (494), Iran (292), Turkey (716), and Uganda (132). Throw a dart at a world map and you are unlikely to hit a spot that has escaped the attention of those who scout out locations for the pharmaceutical industry. The two destinations that one day will eclipse all the others, including Europe and the United States, are China (with 1,861 trials) and India (with 1,457). A few years ago, India was home to more American drug trials than China was, thanks in part to its large English-speaking population. But that has changed. English is now mandatory in China’s elementary schools, and, owing to its population edge, China now has more people who speak English than India does…}

^{One big factor in the shift of clinical trials to foreign countries is a loophole in F.D.A. regulations: if studies in the United States suggest that a drug has no benefit, trials from abroad can often be used in their stead to secure F.D.A. approval. There’s even a term for countries that have shown themselves to be especially amenable when drug companies need positive data fast: they’re called “rescue countries.” Rescue countries came to the aid of Ketek, the first of a new generation of widely heralded antibiotics to treat respiratory-tract infections. Ketek was developed in the 1990s by Aventis Pharmaceuticals, now Sanofi-Aventis. In 2004—on April Fools’ Day, as it happens—the F.D.A. certified Ketek as safe and effective. The F.D.A.’s decision was based heavily on the results of studies in Hungary, Morocco, Tunisia, and Turkey.}

^{The approval came less than one month after a researcher in the United States was sentenced to 57 months in prison for falsifying her own Ketek data. Dr. Anne Kirkman-Campbell, of Gadsden, Alabama, seemingly never met a person she couldn’t sign up to participate in a drug trial. She enrolled more than 400 volunteers, about 1 percent of the town’s adult population, including her entire office staff. In return, she collected $400 a head from Sanofi-Aventis. It later came to light that the data from at least 91 percent of her patients was falsified. [Kirkman-Campbell was not the only troublesome Aventis researcher. Another physician, in charge of the third-largest Ketek trial site, was addicted to cocaine. The same month his data was submitted to the F.D.A. he was arrested while holding his wife hostage at gunpoint.] Nonetheless, on the basis of overseas trials, Ketek won approval…}

^{It used to be that clinical trials were done mostly by academic researchers in universities and teaching hospitals, a system that, however imperfect, generally entailed certain minimum standards. The free market has changed all that. Today it is mainly independent contractors who recruit potential patients both in the U.S. and—increasingly—overseas. They devise the rules for the clinical trials, conduct the trials themselves, prepare reports on the results, ghostwrite technical articles for medical journals, and create promotional campaigns. The people doing the work on the front lines are not independent scientists. They are wage-earning technicians who are paid to gather a certain number of human beings; sometimes sequester and feed them; administer certain chemical inputs; and collect samples of urine and blood at regular intervals. The work looks like agribusiness, not research…}

^{Other private contractors are public companies, their stock traded on Wall Street. Pharmaceutical Product Development [P.P.D.], a full-service medical contractor based in Wilmington, North Carolina, is a public company with 10,500 employees. It, too, has conducted clinical trials all around the world. In fact, it was involved in the clinical trials for Ketek—a P.P.D. research associate, Ann Marie Cisneros, had been assigned to monitor Dr. Anne Kirkman-Campbell’s testing in Alabama. Cisneros later told the congressional investigating committee that Kirkman-Campbell had indeed engaged in fraud. “But what the court that sentenced her did not know,” Cisneros said, was that “Aventis was not a victim of this fraud.” Cisneros said she had reported her findings of fraud to her employer, P.P.D., and also to Aventis. She told the congressional committee, “What brings me here today is my disbelief at Aventis’s statements that it did not know that fraud was being committed. Mr. Chairman, I knew it, P.P.D. knew it, and Aventis knew it.” Following her testimony the company released a statement saying it regretted the violations that occurred during the study but was not aware of the fraud until after the data was submitted to the F.D.A…}

Drug Makers Relied On Two Researchers Who Now Await Trial
The Wall Street Journal Europe
By Steve Stecklow and Laura Johannes
08/18/97

^{Georgia state investigators accuse the two men of running a secret, renegade drug- testing operation, recklessly endangering patients and stealing from Georgia’s only state medical school more than $10 million in drug-company payments. They contend that Dr. Borison, a 47-year-old medical doctor, was rarely around the test sites and left unqualified employees to treat patients and that Dr. Diamond, 52, a pharmacologist, routinely forged Dr. Borison’s signature on patient and test records. Former employees of the pair say they were pressured to enroll large numbers of patients, whether eligible to participate or not…}

^{The two researchers "had been active in the development of many successful drugs, and they were good recruiters," says William Kennedy, vice president of Zeneca Inc., of Wilmington, Delaware, which hired them in 1990 to test Seroquel, a schizophrenia drug. Among other companies, Johnson & Johnson hired the men to test Risperdal, its new schizophrenia medicine, and SmithKline Beecham PLC had them evaluate Paxil, a now-popular antidepressant. Their dozens of other clients also included Bristol-Myers Squibb Co., Eli Lilly Co. and Glaxo Wellcome PLC.}

^{Some Borison-Diamond staffers had no medical training before arriving at the clinic, but were asked to do sophisticated tasks, the FDA and former employees say. Two of their study coordinators had been hired after working as Girl Scout administrators; another had recently been a Delta Airlines flight attendant. At Suite 7, the office secretary became the staff pharmacist, keeping track of experimental drugs; she had no professional training. Christy Hernandez, who began working at BioTech Park as a study coordinator in December 1994, also had no medical training, yet was put to work interpreting electrocardiograms and blood tests — tasks normally done by physicians. She says she was deciding whether Alzheimer’s patients could safely continue taking an experimental Sandoz drug. "There are many intricacies in reading medical data, and I didn’t know how to do it," she says. Answering the telephone, she adds, is "all I should have been doing." Dr. Borison, meanwhile, was rarely in, several former employees say. "He was never at BioTech Park other than for, like, a birthday," says Angela Touey, another former study coordinator.}

^{Ms. Hernandez and other former employees say that Dr. Diamond pressured them to recruit large numbers of test subjects quickly, including some who may not have qualified, and that their pay depended on it. The employees’ low pay was supplemented by frequent bonuses — of $500 or more — that were partly based on the number of patients they recruited. Ms. Brown says Dr. Diamond once wrote on a cocktail napkin that "he would double my salary that year" if she recruited 30 new patients for a Sandoz Alzheimer’s study. Ms. Brown says she barely missed the quota. A contract shows the drug company had offered to pay $19,380 per subject — one of the highest amounts ever offered in an Alzheimer’s trial.}

^{In January 1996, Drs. Borison and Diamond opened a new research site to prospect for subjects in Charlotte, North Carolina. John Stokes, an inspector from Quintiles Transnational Corp., visited it a few months later. Sandoz had hired Quintiles, a medical-research contractor in Research Triangle Park, North Carolina, to help oversee its Alzheimer’s studies, and Mr. Stokes questioned how Dr. Borison could sign records for patients seen in Charlotte on a day when he was nearly 320 kilometers away in Augusta. "The more questions he asked, the more nervous Dr. Diamond got," says a former study coordinator. A person familiar with the matter says Dr. Diamond complained to Mr. Stokes’s superiors at Quintiles. The next business day, Mr. Stokes was off the case. "Poor guy, he got in trouble," says Sharad Mogul, who managed the Charlotte office for Drs. Borison and Diamond at the time and had formerly worked at Quintiles. The drug- testing inspection system, he says, "is a joke, and what happened to John Stokes is a classic example." He says drug companies treat researchers like "kings" and are reluctant to antagonize them because they supply the study data. Mr. Stokes and Quintiles decline to comment…}

^{George Schuster, chairman of the medical school’s institutional review board, says he is still disturbed by the drug companies’ response to the scandal. He notified about two dozen companies in June 1996 that Drs. Borison and Diamond had resigned their positions after allegations of research misconduct and wrote that the school was "very concerned" about patients’ welfare. But many of the companies "didn’t seem particularly concerned" about patients, Dr. Schuster says, adding that most were interested only in whether data had been faked. Told there was no immediate evidence of that, "most of them seemed to lose interest," he says…}