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

Dinavance Kamukama, 28, front right, with her cousins in Kampala, Uganda. She is on a waiting list for AIDS medication.

If anyone is looking to buy the book for a class or symposium – or, of course, for themselves – the cost will be significantly less than the hardback version, narturally.

Please visit my friends at Amazon.com or Barnes & Noble and other major online booksellers below or visit any other site or bookstore where you normally shop to reserve a copy or buy one in the future.

Also in August my first novel, Bad Day for the Home Team, will be released by Zumaya Books. The book is about how a very average man in Sierra Vista, Arizona walks into a pizza place, shoots and kills 30 people, then kills himself. He comes back as a ghost and tries to figure out why he did what he did while a cop, his brother, and a reporter try to also unravel the mystery of “Why he done it?” I will excerpt Bad Day in the weeks before its release and will start visiting sites and groups to talk about the book and others like it. If you have any suggestions for sites that might be good, let me know.

I’ll be posting more about this book and other projects soon.

April 27, 2010

A Genentech Eye Treatment Is Found to Help Prevent Vision Loss in Diabetics

By ANDREW POLLACK

The drug Lucentis can improve eyesight being lost to diabetes, researchers reported on Tuesday, a finding they hailed as a major advance in combating a common cause of blindness.

The finding comes from a large government-sponsored clinical trial that tested the drug, which is made by Genentech, as a treatment for the condition known as diabetic macular edema.

Nearly half the people whose eyes were treated with Lucentis, often in combination with standard laser therapy, had an improvement in vision of at least two lines on an eye chart after one year. That compared with only about 30 percent of those receiving laser therapy alone. And fewer people treated with Lucentis experienced a big loss of vision.

“This is the first new treatment for people with diabetic macular edema in a quarter of a century,” Dr. Frederick L. Ferris III, clinical director of the National Eye Institute, which sponsored the trial, said in a telephone news conference on Tuesday.

He said that at least one million Americans now have diabetic macular edema, and the number is expected to grow with the increasing incidence of diabetes. The condition is one consequence ofdiabetic retinopathy, which is the leading cause of blindness in working-age Americans.

Dr. Neil M. Bressler of Johns Hopkins University, the chairman of the group that conducted the trial, said a two-line improvement in vision would allow some people to read normal-size print or to drive again.

Lucentis is not approved as a treatment for macular edema. But it is approved for another eye disease, age-related macular degeneration.

So doctors can — and some already do — use the drug off-label for the diabetic condition. With this successful Phase 3 trial, insurers will now be more likely to pay for such off-label use.

Some doctors criticized the organizers of the trial for testing Lucentis rather than another Genentech drug, Avastin, which works in the same way as Lucentis.

Although it is a cancer drug, Avastin is often used off-label for eye diseases because it is far cheaper than Lucentis, costing only $20 to $100 a dose, compared with $2,000 for Lucentis.

Avastin is undercutting sales of Lucentis, which totaled $1.1 billion in the United States last year.

Organizers of the trial conceded that a major reason Lucentis was chosen was that Genentech, which is now owned by Roche, agreed to provide the drug free of charge and to contribute $9 million in additional financing — but only if Lucentis were used.

“Obviously you can’t underplay $9 million,” said Dr. Ferris of the eye institute, which is part of the part of the National Institutes of Health. But he said there were other factors as well, like a belief that Lucentis might have been the better drug.

Dr. Philip J. Rosenfeld, a professor of ophthalmology at the University of Miami, said the decision was “clearly a case of pay to play” since Genentech’s money dictated the choice of drugs.

Retinopathy results from damage to the blood vessels in the eye. In macular edema, fluid from those damaged vessels leaks into the macula, the part of the retina that is responsible for the straight-ahead vision important for driving, recognizing faces and reading.

Lucentis, also known as ranibizumab, works by drying up leaky blood vessels and preventing the growth of new ones.

John Bevan, who has diabetic macular edema, said that every two months or so he used to have an incident in which blood leaked into his eye, blurring his vision.

“It’s like a paintball hits a plate-glass window — there’s a big splat and it drips downward and takes three days to a week to dissipate,” said Mr. Bevan, the school superintendent in north central Indiana. He said treatment with Lucentis in the clinical trial virtually eliminated those incidents.

The trial involved 691 patients, some of whom had both eyes treated, resulting in 854 total eyes. There were four treatment groups: One group got Lucentis injections into the eye as often as every four weeks, plus laser therapy. Another got Lucentis, with laser therapy used only after six months and only if needed. The third group got laser therapy plus injections into the eye of triamcinolone, a steroid sold by Allergan under the name Trivaris. The fourth group got laser therapy plus a sham injection.

After the first year, only 3 to 4 percent of the eyes treated with Lucentis suffered a visual loss of two or more lines compared to 13 percent that got only laser therapy.

Researchers said the results seem to be holding up for the second year of the three-year trial.

About 1 percent of those getting Lucentis injections suffered an inflammation of the eye from an infection.

The steroid treatment did not improve eyesight more than laser therapy alone and caused side effects.

Results of the trial were published online on Tuesday by the journal Ophthalmology.

Impact of Privacy Rules on Research

Gay And Lesbian Patients Excluded From Some Clinical Trials

18 Mar 2010

All clinical trials have guidelines that clearly state who can and cannot participate, but according to the National Institutes of Health these guidelines are typically based on age, gender, previous treatment history, the type and stage of a disease, and other medically relevant factors. However, researchers at Fox Chase Cancer Center have gathered evidence indicating that some trials explicitly exclude individuals based on their sexual orientation. Their findings are published in a research letter appearing in the March 18 issue of the New England Journal of Medicine.

By performing exploratory searches of ClinicalTrials.gov – a site containing detailed information on over 80,000 clinical trials sponsored by the National Institutes of Health, other governmental agencies, and private industry – for explicit inclusion and exclusion criteria that required participants to be in heterosexual relationships, Brian Egleston, Ph.D., an assistant research professor of biostatistics and bioinformatics at Fox Chase, and colleagues found that exclusion of lesbians and gay men from clinical trials in the United States is not uncommon, particularly in studies with sexual function as an endpoint. His coauthors included Fox Chase Cancer Center researchers Roland Dunbrack, Jr., Ph.D., and Michael Hall, M.D.

“Most gay and lesbian patients are probably unaware that their sexual orientation is being used as a screening factor for clinical trial participation”, notes Egleston. “This is a potentially significant issue, both for patients and the medical research community.”

The searches, which included only trials with sites in the United States, showed that 15 percent of the identified studies using the terms “erectile dysfunction,” “couples,” and “hypoactive” had exclusionary language. In addition, the results indicated that industry sponsored trials, multi-region trials, and Phase III trials were more likely to exclude lesbians and gay men among these studies.

“The trials that exclude gay and lesbian patients tend to be larger efficacy clinical trials. Further, by requiring patients to be in heterosexual relationships, many studies are also excluding unmarried or unpartnered patients regardless of sexual orientation,” says Dunbrack.

To ensure that there was not a general pattern of exclusionary language missed, the researchers also looked at 1,019 studies identified by the search term “asthma.” This search did not find any studies that excluded lesbians and gay men.

Source:
Diana Quattrone
Fox Chase Cancer Center