Here’s a link to the pdf and the review is below.

Chasing Medical Miracles: The Promise and Perils of Clinical Trials.

By Alex O’Meara. 264 pp. New York,

NY: Walker and Company. 2009. $25.00 (cloth),

$16.00 (paper).

O’Meara immediately caught my attention, when he noted that the number of clinical

trials worldwide has increased 300% since 1998 and 20 of 50 million clinical trial

participants live in the United States. O’Meara tells two stories in Chasing Medical

Miracles. The first is a critical evaluation of clinical trials and their slow but perhaps

steady contributions to scientific progress in medicine and human biology, and the other

story is about the author who wanted to cure his worsening type 1 diabetes by

participating in a clinical trial. I could not put this book down.

He says on page 3 of the introduction that he does not ‘‘advocate for or against

clinical trials’’ but instead desires to simplify the complex clinical trial business for

readers. He also views the clinical trials of today to anticipate aspects of future US

medical care.

Chapter 1 details what it means to volunteer for a trial or to become a ‘‘guinea

pig.’’ Chapter 2 is a spectacular discussion of the ‘‘therapeutic misconceptions’’ that

guinea pigs have, and the history of (e.g., Josef Mengele and Tuskagee) and the ethical

issues that arise when people are experimental subjects. Chapter 3 follows the money and

describes how clinical trials were initially dominated by universities that have been partly

replaced by more ‘‘efficient’’ private businesses and the conflicts of interest that can put

clinical trial participants at risk. (I also wondered about the drain of personnel from

patient care at this time of acute shortages in general practitioners, nurses, etc.)

Chapter 4 details a few of the lawsuits that have ensued.

Chapter 5 describes the typical subjects of these clinical trials from hopeful

individuals with health problems to the professional guinea pigs who may not represent

your average person anywhere. (What does that mean for medication dosages?)

Chapter 6 critiques how the business of trials has moved from the United States to

other nations in which human subjects protection can be weaker than in the United States

(e.g., the continuing use of placebos rather than comparing standard treatment protocol to

experimental protocol).

Uganda is the focus of Chapter 7 and serves as a model for a sophisticated effort

to grapple with the ethical issues and the logistics of monitoring and enforcing rules

during clinical trials.

Chapter 8 explains why specific individuals participate in clinical trials; O’Meara

includes success stories as well as failures. The book finishes with his personal

experience participating in a clinical trial to receive pancreatic islet cells from several

deceased donors. He was not cured, but he ends his tale and the critique of clinical trials

on a cautiously positive note.

This book is a must read for those contemplating volunteering for a clinical trial

(advice in the Afterward), and it also provides discussion starting points for those who

teach classes on ethics in research and medicine, global health, the pharmaceutical

industry, and the business of medical research.

JOAN C. STEVENSON

Department of Anthropology

Western Washington University

Bellingham, Washington

I spoke to one of the Al Jazeera producers for this segment when the story was being developed. They were originally intending to go to Africa, and maybe even Uganda, where I conducted research, but instead went to India. The stories told about trials in India in the segment are similar to stories I wrote about and researched while in Africa.

It’s worth a look if you’re interested in what is an emerging healthcare crisis and a fascinating topic.

watch?v=g_p0kmrFi_o

The site is owned by a company called TrialX, which, apparently, is less scary than it sounds. The statement of their purpose on their site says:” TrialX is developed by Applied Informatics Inc., a New York based company with extensive experience in the areas of Health Information Technology, Computer Science, Medicine and Clinical Research. Besides the qualifications, our team has balanced bold thinking and new ideas with real-world challenges in the healthcare industry.”

Their site is worth a look, as are their tweets. TrialX is at the forefront of a new model for marketing trials – which is good or bad, depending on your point of view of such things. They are a company that uses Twitter to reach out to deliver information about trials to people who may wish to enroll. They have integrated with Google Health and Microsoft’s HealthVault in order broaden their patient reach – and also to have a massive database of individuals they can market to.

This is another example of how the big business of clinical trials keeps getting bigger and bigger every day.

The reality is 99 percent of all clinical trials and experiments in the United States are ethical, controlled, proper, and successful. Most are necessary from a medical standpoint, although far too many are being conducted to develop “products” to maintain corporate stock prices. It stands however, that because medical experimentation is so rife with drama and impact on the human psyche that the small percentage that is reprehensible and retrograde resonates powerfully. It’s as it should be. The clinical trials community should take a moment and consider a comprehensive way to comunicate the good they do; or at leas, in this instance, respond with proper outrage and indignation that this chapter is sullying the fine work being conducted now.

October 1, 2010

U.S. Apologizes for Syphilis Tests in Guatemala

By DONALD G. McNEIL Jr.

From 1946 to 1948, American public health doctors deliberately infected nearly 700 Guatemalans — prison inmates, mental patients and soldiers — with venereal diseases in what was meant as an effort to test the effectiveness of penicillin.

American tax dollars, through the National Institutes of Health, even paid for syphilis-infected prostitutes to sleep with prisoners, since Guatemalan prisons allowed such visits. When the prostitutes did not succeed in infecting the men, some prisoners had the bacteria poured onto scrapes made on their penises, faces or arms, and in some cases it was injected by spinal puncture.

If the subjects contracted the disease, they were given antibiotics.

“However, whether everyone was then cured is not clear,” said Susan M. Reverby, the professor at Wellesley College who brought the experiments to light in a research paper that prompted American health officials to investigate.

The revelations were made public on Friday, when Secretary of State Hillary Rodham Clinton and Health and Human Services Secretary Kathleen Sebelius apologized to the government of Guatemala and the survivors and descendants of those infected. They called the experiments “clearly unethical.”

“Although these events occurred more than 64 years ago, we are outraged that such reprehensible research could have occurred under the guise of public health,” the secretaries said in a statement. “We deeply regret that it happened, and we apologize to all the individuals who were affected by such abhorrent research practices.”

In a twist to the revelation, the public health doctor who led the experiment, John C. Cutler, would later have an important role in the Tuskegee study in which black American men with syphilis were deliberately left untreated for decades. Late in his own life, Dr. Cutler continued to defend the Tuskegee work.

His unpublished Guatemala work was unearthed recently in the archives of the University of Pittsburgh by Professor Reverby, a medical historian who has written two books about Tuskegee.

President Álvaro Colom of Guatemala, who first learned of the experiments on Thursday in a phone call from Mrs. Clinton, called them “hair-raising” and “crimes against humanity.” His government said it would cooperate with the American investigation and do its own.

The experiments are “a dark chapter in the history of medicine,” said Dr. Francis S. Collins, director of the National Institutes of Health. Modern rules for federally financed research “absolutely prohibit” infecting people without their informed consent, Dr. Collins said.

Professor Reverby presented her findings about the Guatemalan experiments at a conference in January, but nobody took notice, she said in a telephone interview Friday. In June, she sent a draft of an article she was preparing for the January 2011 issue of the Journal of Policy History to Dr. David J. Sencer, a former director of the Centers for Disease Control. He prodded the government to investigate.

In the 1940s, Professor Reverby said, the United States Public Health Service “was deeply interested in whether penicillin could be used to prevent, not just cure, early syphilis infection, whether better blood tests for the disease could be established, what dosages of penicillin actually cured infection, and to understand the process of re-infection after cures.”

It had difficulties growing syphilis in the laboratory, and its tests on rabbits and chimpanzees told it little about how penicillin worked in humans.

In 1944, it injected prison “volunteers” at the Terre Haute Federal Penitentiary in Indiana with lab-grown gonorrhea, but found it hard to infect people that way.

In 1946, Dr. Cutler was asked to lead the Guatemala mission, which ended two years later, partly because of medical “gossip” about the work, Professor Reverby said, and partly because he was using so much penicillin, which was costly and in short supply.

Dr. Cutler would later join the study in Tuskegee, Ala., which had begun relatively innocuously in 1932 as an observation of how syphilis progressed in black male sharecroppers. In 1972, it was revealed that, even when early antibiotics were invented, doctors hid that fact from the men in order to keep studying them. Dr. Cutler, who died in 2003, defended the Tuskegee experiment in a 1993 documentary.

Deception was also used in Guatemala, Professor Reverby said. Dr. Thomas Parran, the former surgeon general who oversaw the start of Tuskegee, acknowledged that the Guatemala work could not be done domestically, and details were hidden from Guatemalan officials.

Professor Reverby said she found some of Dr. Cutler’s papers at the University of Pittsburgh, where he taught until 1985, while she was researching Dr. Parran.

“I’m sifting through them, and I find ‘Guatemala … inoculation …’ and I think ‘What the heck is this?’ And then it was ‘Oh my god, oh my god, oh my god.’ My partner was with me, and I told him, ‘You aren’t going to believe this.’ ”

Fernando de la Cerda, minister counselor at the Guatemalan Embassy in Washington, said that Mrs. Clinton apologized to President Colom in her Thursday phone call. “We thank the United States for its transparency in telling us the facts,” he said.

Asked about the possibility of reparations for survivors or descendants, Mr. de la Cerda said that was still unclear.

The public response on the Web sites of Guatemalan news outlets was furious. One commenter, Cesar Duran, on the site of Prensa Libre wrote: “APOLOGIES … please … this is what has come to light, but what is still hidden? They should pay an indemnity to the state of Guatemala, not just apologize.”

Dr. Mark Siegler, director of the Maclean Center for Clinical Medical Ethics at the University of Chicago’s medical school, said he was stunned. “This is shocking,” Dr. Siegler said. “This is much worse than Tuskegee — at least those men were infected by natural means.”

He added: “It’s ironic — no, it’s worse than that, it’s appalling — that, at the same time as the United States was prosecuting Nazi doctors for crimes against humanity, the U.S. government was supporting research that placed human subjects at enormous risk.”

The Nuremberg trials of Nazi doctors who experimented on concentration camp inmates and prisoners led to a code of ethics, though it had no force of law. In the 1964 Helsinki Declaration, the medical associations of many countries adopted a code.

The Tuskegee scandal and the hearings into it conducted by Senator Edward M. Kennedy became the basis for the 1981 American laws governing research on human subjects, Dr. Siegler said.

It was preceded by other domestic scandals. From 1963 to 1966, researchers at the Willowbrook State School on Staten Island infected retarded children with hepatitis to test gamma globulin against it. And in 1963, elderly patients at the Brooklyn Jewish Chronic Disease Hospital were injected with live cancer cells to see if they caused tumors.

That’s was partly why when I read in the NYT article that some cancer experts thought a new wave of experimental cancer drugs should be used for treatment before they’re approved I sat stunned. I read the article three times. “Experts” are actually arguing that patients should have increased access to drugs not yet tested and that this should be done on compassionate grounds. This article, by the way, came out a few days before the FDA decided to restrict Avandia, a drug that HAD ALREADY BEEN APPROVED because it increased the likelihood of heart attack

The very first time I saw the words “therapeutic misconception” in the New York Times was just one month ago. In an article by Gina Kolata, What to Tell the Patient After a Trial Goes Awry. “Most patients entering clinical trials believe they are getting a new treatment that may benefit them, Dr. Brody [director of the Center for Medical Ethics and Health Policy at Baylor College of Medicine said]said. Ethicists call that a ‘therapeutic misconception,’ he said, adding, ‘No one should ever assume that in a clinical trial.”

Gosh, ya think?

Like most media outlets, the Times treats trials as another medical option available to patients. This is because patients consider trials a medical option; as if they’re getting to buy wholesale rather than retail. That’s because doctors and researchers encourage patients to think of them as an option so they can recruit subjects to trials. It’s one vast belief but it’s not true. It’s built on statistics: If enough people believe it, eventually it’s true. I used to believe that truth was not statistical, that popularity didn’t make a thing real. And, of course, in an activity as rigorous about process and facts as medical research, truth was surely an inflexible concept. But after reading the NYT article I realized some researchers want the truth to be flexible, based on the whims of doctors and patients. And that’s a great way to make the truth disappear.

Click here for direct to NYT coverage.

Blogging the F.D.A. Panel on Avandia

Dr. Elaine Morrato, a panel member and an assistant professor at the University of Colorado, asked about worries that Actos might increase the risks of bladder cancer.

Dr. Mary H. Parks of the F.D.A. answered that animal trials had suggested there might be a cancer risk in the bladder. And she said that large trials of Actos did not dismiss that risk. But she said similar drugs in the same class have all suggested that the drugs might have a cancer risk.

Rebecca Killion, a panel member, asked whether Avandia might still be appropriate for patients with few cardiovascular risks.

Younger patients, for instance, are not nearly as susceptible to heart attacks as older ones. Her question led to a small debate between Dr. Steven Nissen, the Cleveland Clinic cardiologist who has advocated Avandia’s withdrawal, and Dr. Philip Home, who led the Avandia Record trial and has said that his research is funded by GlaxoSmithKline.

Dr. Nissen argued that no diabetic is without risk for cardiovascular disease.

“Not only are diabetics getting younger, but diabetics with coronary disease are getting younger,” Dr. Nissen said. “To say that there’s some diabetic that’s not at risk, is probably not something we can parse.

Dr. Home responded he routinely makes such decisions in his clinical practice. For instance, since both Avandia and Actos increase the risks of fracture, he would not give either drug to patients with osteoporosis, he said. “We would certainly target these drugs to certain groups of people,” Dr. Home said.

After a brief debate about whether the questions they will be asked to vote upon are appropriate, the committee’s members have moved into an hour of discussions and questions.

This is the time that we will begin to see how the committee is moving, and these sorts of discussions can sway uncertain panelists.

After only a handful of speakers, the public hearing ended.

Dr. Gerald Dal Pan, director of F.D.A.’s Office of Surveillance and Epidemiology, is now explaining to the committee what the advisers are supposed to do.

His message is a bit like the charge that a judge gives a jury before they consider a case. But the fact that Dr. Dal Pan is making this speech is interesting. Dr. Dal Pan is the leader of a group of review officials who have advocated forcefully for Avandia’s removal from the market. During the meeting, he has been sitting next to Dr. John Jenkins and Dr. Janet Woodcock, two F.D.A. officials who have defended Avandia’s continued sales.

The agency’s internal conflicts have been on stark display during this advisory committee meeting. But Dr. Dal Pan’s calm and even-handed presentation may be intended to signal that agency officials can work well together despite their differences.

Dr. Dal Pan assured the committee that their views are important to the agency.

“A transcript is made of these meetings, and we actually do go back and read them,” Dr. Dal Pan said. “We are very interested in the rationale for your vote.”

Jackie Bosch is reading a letter written by Dr. Salim Yusuf of McMaster University, who is a principal investigator of the Tide trial, the test comparing Avandia with Actos.

Public testimony is generally given directly, but this hearing has been unusual for several reasons.

In his letter, Dr. Yusuf bemoans the discussion in both the media and the medical literature about Avandia’s risks, saying that it has been based on poor science. He argued that only trials like the one he is in the midst of conducting can definitively answer questions about drug safety.

The public part of the advisory meeting has begun, and like so much about this meeting, it is unusual.

In many of these meetings, the public part of the meeting is made up of a collection of unsophisticated patients and doctors who tell poignant and personal stories about their experiences with a drug. But the first several public speakers for this meeting came with PowerPoint slides and sophisticated arguments about the underlying trials.

Dr. Christopher McCoy, a hospitalist at the Mayo Clinic in Minnesota, Minn., and a representative of the National Physicians Alliance, spoke about the effects that financial connections with drug makers can have on interpretations of studies. He was followed by Dr. Hal M. Roseman, who consults for GlaxoSmithKline, and amid a set of slides with pictures of the comedian David Letterman, offered a complicated set of slides defending Avandia’s continued sales.

Then came Diana Zuckerman, president of the National Research Center for Women and Families, whose slides emphasized Avandia’s dangers.

Many more speakers are coming.

GlaxoSmithKline’s reputation has been battered throughout this advisory committee hearing, and it took another hit a moment ago.

Dr. William Knowler, a panel member who is chief of diabetes epidemiology at the National institute of Diabetes and Digestives and Kidney Diseases, described a key analysis done by GlaxoSmithKline as “totally incorrect and deceptive.”

Dr. Dean Follman, a mathematician at the National Institute of Allergy and Infectious Diseases, agreed that the company’s analysis was incorrect.

“I don’t know if I would term it as deceptive,” Dr. Follman said. But since the company failed to explain why it conducted its analysis so poorly “I would ignore it, basically,” he said.

The Food and Drug Administration hearing on Avandia, the controversial diabetes drug, is under way. A complex set of votes is expected later today on whether to remove the drug from the market because of the risk for heart attacks.

Dr. Hertzel Gerstein, a professor at McMaster University who is in charge of an ongoing study comparing the safety of Avandia and Actos, started today’s hearing with a passionate defense of ethics of the study, which has been dubbed the “Tide trial.”

Nearly shouting into a microphone, Dr. McMaster said that experts who called the trial unethical on Tuesday were mistaken.

“In the next 20 minutes, I hope to correct the misperceptions that were repeated yesterday and to show you that TIDE is both appropriate and needed,” he said.

One presenter on Tuesday claimed that the TIDE trial is largely being conducted in the Third World because doctors in the United States are not comfortable with putting patients in the trial.

“Contrary to what was stated yesterday, this study is mainly being conducted in the developed Western world,” Dr. Gerstein said.

We’ll be updating this post throughout the hearing with the latest developments

July 14, 2010

Panel to Rule on Safety of Diabetes Drug

GAITHERSBURG, Md. — A federal advisory panel will vote Wednesday on whether Avandia, a controversial diabetes medicine, is safe enough to remain on the market.

The panel heard a raft of conflicting scientific information on Tuesday not only from Avandia’s maker, GlaxoSmithKline, but also from feuding scientists within the Food and Drug Administration. An important issue is whether information from clinical trials conducted by GlaxoSmithKline can be believed. On Tuesday, panel members heard evidence that patients in a crucial trial of Avandia who suffered heart attacks did not have their problems included in the trial’s final tally. And internal company documents made public in recent days show that the company hid from the public crucial information about Avandia’s safety woes.

Some reviewers within the F.D.A. said Tuesday that studies demonstrate conclusively that Avandia is far more dangerous to the heart than a similar medicine, Actos, made by Takeda. But other reviewers said that the trials are far more equivocal and provide little evidence that Avandia is dangerous. Scientists at GlaxoSmithKline argued that Avandia is a safe and important option in the treatment of Type 2 diabetes.

Questions from some panel members on Tuesday hinted that skepticism about GlaxoSmithKline’s trustworthiness is shared by at least some of the advisers. But with most of the scientific presentations completed on Tuesday, panel members are expected to give far greater voice to their own views on Wednesday. A series of complex votes are scheduled for the afternoon.

As a diabetic who volunteered for a risky transplant to cure my condition, I completely empathize with MS patients profiled in the New York Times piece below who are pushing to have increased access to unproven treatments for their condition. It’s only natural to want to be cured or at least make a worthwhile attempt at a cure.

As an expert in clinical trials though I have to say this trend where patients increasingly drive the focus of research and the availability of unproven treatments is absurd, insane, and potentially life-threatening. To have laypeople at the table with those deciding the course of future treatments and of what will be tested is a great idea. To have those same people begin to dictate research priorities is dangerous in the short-term and counter-productive to developing legitimate treatments in the longterm.

No matter how heart wrenching these personal stories, anecdote and desperation should never  be a significant factor in conducting effective clinical trials. It makes for bad research and produces bad medicine.

From M.S. Patients, Outcry for Unproved Treatment

Béatrice de Géa for The New York Times

By DENISE GRADY

Published: June 28, 2010

For her first appointment with Dr. Daniel Simon, Neelima Raval showed up with a rolling file cabinet full of documents. She had downloaded every word written by or about Dr. Paolo Zamboni, a vascular surgeon from Italy with a most unorthodox theory about multiple sclerosis.

Dr. Zamboni believes that the disease, which damages the nervous system, may be caused by narrowed veins in the neck and chest that block the drainage of blood from the brain. He has reported in medical journals that opening those veins with the kind of balloons used to treat blocked heart arteries—an experimental treatment he calls the “liberation procedure”— can relieve symptoms.

The idea is a radical departure from the conventional belief that multiple sclerosis is caused by a malfunctioning immune system and inflammation.

The new theory has taken off on the Internet, inspiring hope among patients, interest from some researchers and scorn from others. Supporters consider it an outside-the-box idea that could transform the treatment of the disease. Critics call it an outlandish notion that will probably waste time and money, and may harm patients.

These critics warn that multiple sclerosis has unpredictable attacks and remissions that make it devilishly hard to know whether treatments are working — leaving patients vulnerable to purported “cures” that do not work.

The controversy has exposed the deep frustration of many people with this incurable, disabling disease, who feel that research has let them down. It is a case study in the power of the Internet to inform and unite angry patients—which may be a double-edged sword. Pressure from activists helped persuade the Multiple Sclerosis Society to pay for studies of Dr. Zamboni’s theory, but the Internet buzz has also created an avid market for a therapy that is still unproved.

“It’s eye-opening the way this group of patients has grabbed hold of the social-networking technology,” said Dr. Simon, an interventional radiologist at JFK Medical Center in Edison, N.J. “They’ve taken this to a level I’ve not seen in other patients. Patients used to read an article or two. Now, they’re actually seeing procedures on YouTube. Is this the future of medicine?”

Scientifically, the jury is out: Dr. Zamboni’s hypothesis is being studied. It is not known whether narrowed veins are more common in people with multiple sclerosis than in others, and even if they are, whether the narrowings are a cause, or an effect, of the disease. There is no solid proof that opening the veins can help. There have been no studies with control groups — the only way to find out whether a treatment works.

“In my view the evidence is quite scanty and the biological plausibility is low,” said Dr. Stephen L. Hauser, the chairman of neurology at the University of California, San Francisco. Many neurologists agree. Dr. Hauser said there was much stronger evidence that the disease arose from genetic variations affecting the immune system.

But Dr. Adnan H. Siddiqui, part of a team at the University at Buffalo that has been studying Dr. Zamboni’s theory, said that it made sense and that the data from Italy was encouraging. Still, he emphasized that more study was needed, and that patients should not be treated until the research was done.

In Demand

Despite the lack of proof, many patients are captivated by the idea that multiple sclerosis might turn out to be a vascular disease. They want to believe it can fixed with a relatively simply procedure, and they want to be tested and treated. Now.

These patients say they cannot afford to wait for research results because they will wind up in wheelchairs before the studies are done. Their only option so far has been a lifelong course of drugs with limited benefits and harsh side effects. To some, balloon treatment seems no riskier than those drugs.

Dr. Zamboni himself has said that the procedure should not yet be done outside of studies. He said in an interview that he was conducting research only and had turned down thousands of requests from people wanting to go to his clinic at the University of Ferrara.

But other doctors have set up shop. A clinic in India with a toll-free American phone number has an online advertisement for a “liberation package.” Patients are posting testimonial videos and trading tips on clinics in Bulgaria, Poland and Jordan.

In the United States, where many hospitals forbid experimental treatments outside of studies, a “back alley” network of doctors willing to perform the procedure has begun to develop, said Dr. Salvatore J. A. Sclafani, chairman of radiology at Downstate Medical Center in Brooklyn. He said he knew of about a dozen. The doctors try to stay under the radar, and patients quietly pass their names to one another.

“It reminds me of abortion in 1968,” Dr. Sclafani said.

He said he had treated about 20 patients at Kings County Hospital before the hospital ordered him to stop in early April. He said he had a waiting list of 300 to 400 patients..

Meanwhile, researchers are trying to answer basic questions. On June 29, the team in Buffalo is to begin the first treatment study to include a control group. The controls will be given a sham procedure, and compared with others who get the real thing. Initially, 30 patients — only those with an early form of the disease — will be enrolled. Thousands of people applied.

The Multiple Sclerosis Societies in the United States and Canada will spend $2.4 million over the next two years on studies at seven centers. Researchers will study veins in patients with different stages of multiple sclerosis, in healthy people and in those with other neurological diseases. The studies will not test the balloon treatment, but are meant only to find out if the narrowings really exist, if they are related to the disease and if they are a cause or an effect.

Some patients complain that the society has been too slow to consider the new idea. A splinter group — the Reformed Multiple Sclerosis Society — has formed to increase the availability of the vein treatment.

Joyce Nelson, the president of the Multiple Sclerosis Society in the United States, said, “I wasn’t aware how thin the veneer was and how close to the surface the frustration was.”

“ ‘We can’t wait’ has resounded,” Ms. Nelson said. But she added, “There isn’t a way to rush the work that needs to be done.”

As the procedure has caught on in some places, few serious complications have been reported. But at Stanford University, a woman, 50, treated with stents (wire-mesh tubes used to hold blood vessels open) and blood-thinning drugs, died of a brain hemorrhageafter returning home, and another patient needed heart surgery after a stent placed in a neck vein came loose and was swept into the heart. The procedures were stopped.

Dr. Michael Dake, who treated the patients, declined several requests for an interview, but said by e-mail that he hoped to discuss “a number of exciting developments” about the procedure “in the near future.”

Dr. Philip Pizzo, the dean of Stanford’s medical school, said the vein theory “deserves to be explored” — but only in studies. A study with a control group is being planned.

About 400,000 people in the United States have multiple sclerosis; worldwide, there are 2.1 million. (The disease is more common in temperate zones than in the tropics, and affects more women than men and more Caucasians than members of other groups.) It usually begins in young adults, with fatigue, vision problems, numbness, bladder trouble and difficulty with walking, balance and coordination. The disease eats away a fatty substance, myelin, that coats nerves, and gradually scars the nerves. The damage is thought to occur because the immune system, for unknown reasons, mistakenly attacks myelin.

Most patients, 85 percent, start out with a form called relapsing-remitting. In about half of those the disease becomes progressive, harder to treat and more disabling. Ms. Raval, who is 38 and has had multiple sclerosis for 13 years, implored Dr. Simon to test her for narrowed veins and, if he found any, to open them.

Dr. Simon regularly uses balloons and stents to open bile ducts and blood vessels. He was impressed with Ms. Raval’s determination, her trove of information and her background. She has a degree in toxicology and works for a drug company. But he was also familiar with Dr. Zamboni’s work—and deeply skeptical of it.

“My initial take was, it doesn’t make any sense,” Dr. Simon said.

But Ms. Raval had high hopes. She said she believed that the balloon treatment would be “the next best thing to a cure.” The usual drugs have not worked for her. Her 5-year-old son is eagerly awaiting the day when she can run with him, but she is finding it harder and harder even to walk.

Theory Born of Experience

Dr. Zamboni, 53, (no relation to the inventor of the ice-rink machine) began studying the medical literature on multiple sclerosis in 1995 when his wife learned she had the disease.

“What I found was like a detective story,” he said.

He discovered reports of vein abnormalities and of brain lesions forming around veins. But the research had been abandoned. Vein disorders are his specialty; he has been studying them for 25 years. He began using ultrasound and other imaging techniques to examine veins, and found narrowings in the neck and chest veins in people with the disease, but not in healthy ones. He suspected that abnormal blood flow and pressure in the veins— not just narrowing alone — might cause minute amounts of bleeding in the brain, leading to an immune reaction and inflammation that damaged myelin and nerves. Iron deposits could also form, and add to the damage. He wondered if opening the narrowed areas might help.

In 2006 he began using balloons to treat patients, including his wife, whose symptoms went away and, he says, have not come back. Other patients who, like his wife, had relapsing-remitting disease, also recovered fully, he said; but some did not respond at all. In those with progressive disease, fatigue improved, but not mobility problems, according to a pilot study he published in December in The Journal of Vascular Surgery. And in half the treated patients, the neck veins closed up again. The study did not have a control group, and the patients were also taking drugs to treat multiple sclerosis . More rigorous trials will start in Italy this summer, Dr. Zamboni said.

Another doctor, Marian Simka, who has been performing the procedure in Pszczyna, Poland, has reported that it has made symptoms worse in some patients..

Researchers in Buffalo have confirmed (but not yet published) that narrowed veins and abnormal blood flow are more common in people with multiple sclerosis. But, while Dr. Zamboni found them in all patients and no healthy people, the Buffalo team found them in about 60 percent of patients and 15 percent of healthy controls.

Granting a Patient’s Wish

Dr. Simon sensed that Ms. Raval would have no peace unless she could learn whether she had narrowed veins, and he wanted to help her.

So he offered to perform a test to find out, a venogram. It involves passing a tube into a vein in the groin and up to the neck and chest, and then injecting dye to take X-rays of the veins. He felt sure there would be no blockages.

“And then she would be able to stop obsessing over this and move on with her life and get some kind of conventional treatment,” he said.

But he was stunned to find narrowings, right where Dr. Zamboni’s theory predicted: in the jugular vein in the neck, and the azygous, a vein in the right side of the chest.

Ms. Raval was elated. She felt certain that opening up those veins would solve her problems. Dr. Simon agreed to try.

Although it was, technically, an experimental procedure, Dr. Simon said he did not have to ask his hospital for permission to perform it. The details were similar to other procedures that interventional radiologists do every day. It is not uncommon for them to take a device approved for one purpose and use it for another, like putting a bile-duct stent into a blood vessel — a practice called “off-label” use, which the Food and Drug Administration allows. Interventional radiology, Dr. Simon said, is an “off-label specialty” that depends on innovation and adaptability.

On March 24, as Ms. Raval lay on a padded table in a treatment room, Dr. Simon passed balloons to the pinched spots in her right jugular and azygous, and dilated them.

The procedure took less than an hour. In the recovery room, Ms. Raval said she felt better already.

Over the next days and weeks, she noticed remarkable improvements. Her fatigue went away. She walked and climbed stairs more easily, and the color in her face brightened. Her husband and co-workers saw the changes, too, she said.

Was it real, or just one giant, communal placebo effect? Ms. Raval posted exuberantFacebook messages naming her “most amazing doctor.” Other patients began calling Dr. Simon.

Within a month, Ms. Raval again had trouble walking. She felt sure her veins had closed again. Another venogram showed they had. Dr. Simon reopened them.

Ms. Raval felt better — and then deteriorated again. On June 18, another venogram, her fourth invasive procedure in three months, suggested that the narrowings had recurred. She struggled over what to do. She could not keep having balloon procedures again and again. Dr. Simon consulted Dr. Dake, his former mentor, who recommended stents.

Initially, Ms. Raval and Dr. Simon had thought stents too risky. Unlike balloons, which are inserted briefly and removed, stents are permanent. They can migrate to somewhere they do not belong, like the heart, as occurred in Dr. Dake’s patient. Or tissue growth can clog them.

But Dr. Simon and Ms. Raval could see no other option. On June 23, he implanted a stent in her two jugular veins.

“I really have a good feeling on this one,” Ms. Raval said a few hours after the procedure. “ I think this is the resolution, long-term. Let’s wait and see.”

In the meantime, Dr. Simon had conducted venograms on about 20 other patients with multiple sclerosis. He found narrowed veins in all but one. He said he was going to ask the hospital’s ethics panel for permission to perform balloon procedures in those patients. But the hospital would have to figure out how to get paid: insurance might cover venograms, but not an experimental treatment. The total charge for the procedure, including both hospital and doctor fees, would be about $10,000, Dr. Simon said.

He and his partner, Dr. Noam Eshkar, said they knew many researchers thought patients should not be given unproven treatments outside of clinical trials. They said they did not disagree. But they also sympathized with patients who had progressive diseases and who felt they did not have the time to wait. “In the real world,” Dr. Eshkar said, “things happen at the edge of scientific proof.”

Nowhere in this article is there any mention of protecting patients from or informing patients about physicians who may have a financial interest in an ongoing trial; either through investment or because drug manufacturers are paying doctors a fee or ”bounty” for every subject they recruit into the trial. The potential for conflicts of interest and abuse of patient confidentiality in the name of easy returns for doctors and drug companies is enormous with this new initiative. Anyone who doesn’t recognize that is either willfully ignoring how some trials function or stands to make a profit off the new, streamlined method of going into confidential patient records to recruit subjects into trials,

• NEW YORK
• JUNE 17, 2010

New Effort Launched for Clinical Drug Trials

By SHIRLEY S. WANG

New York state medical centers and drug makers are launching an initiative to address a nettlesome problem for clinical drug trials: getting patients to sign up.

More than 3,000 clinical trials are actively recruiting in New York state, and an additional 8,000 trials involving New York are already running or were recently completed, according to the government clinical trials registry. Patient recruitment is one of the top reasons that clinical trials are delayed or fail, according to the Tufts Center for the Study of Drug Development.

The new collaboration, known as the Partnership to Advance Clinical electronic Research, or Pacer, aims to create a more systematic way of identifying patients for trials by utilizing the electronic patient medical records that many medical centers already use, according to David Krusch, chairman of the Pacer leadership group and chief medical information officer at Strong Memorial Hospital in Rochester.

Currently, the methods used to enroll patients are “very manual” and “cumbersome,” says Dr. Krusch. Typically, trial operators would recruit patients from a hospital or medical center by hanging fliers in the cafeteria or in waiting rooms. The haphazard method often doesn’t yield the right patients or an adequate number in the needed time frame, according to Dr. Krusch.

Methods for patient recruitment have improved over time with more companies making use of recruitment specialists or patient databases, but “there is a lot of hype,” said Ken Getz, a senior research fellow at the Tufts Center who isn’t involved in the New York collaboration. Sometimes an approach works for one study and not another, he said.

Under the new effort, if a patient meets the inclusion standards for a clinical trial, the system would electronically alert the patient’s doctor. The physician could then ask the patient if he or she was interested in participating. Ultimately, the goal is to link up medical center databases across the region.

“Patients aren’t always aware that opportunities are available,” said Dr. Krusch.

To protect patient confidentiality, only the patient’s doctor would be alerted to the potential eligibility for a trial, and the patient would have to give consent, according to Kathleen Ciccone, executive director of the Healthcare Association of New York State, a nonprofit that represents health-care organizations and hospitals and is part of the Pacer coalition.

The Pacer group also includes the Hastings Center, a nonprofit bioethics group, and several medical centers and health-information technology companies.

The group, which says it receives funding from drug makers and health information-technology firms, hopes to come up with standard protocols for clinical-trial eligibility within the next six to 12 months and start rolling out some of the changes two years after that.

Write to Shirley S. Wang at shirley.wang@wsj.com

Kids in CA Trials Lack Understanding of Research

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