Sunday, July 29, 2012

Doctors Petition for Limits on Painkillers - NYTimes.com

A group of doctors and public health officials urged the Food and Drug Administration on Wednesday to curtail the overuse and abuse of prescription painkillers by changing labeling directions on how and when physicians should prescribe them.

The request came in a so-called citizens petition sent Wednesday to the F.D.A. by some 35 physicians, including Dr. Thomas A. Farley, the commissioner of the Department of Health in New York City, and Dr. Nirav R. Shah, the commissioner of the New York State Department of Health.

The F.D.A. rarely acts on the basis of such petitions, and it can take months or years for the agency to respond. However, the move by the group appears to be part of a broader campaign by public health officials to highlight the dangers posed by narcotic painkillers, or opioids, particularly when they are used at high dosages or over long periods of time.

"Overprescribing of opioids is harming many chronic pain patients," Edward Covington, director of the Neurological Center for Pain at the Cleveland Clinic, said in a statement.

Currently, narcotic painkillers are approved by the F.D.A. for use in the treatment of "moderate to severe" pain.

The drugs fall into two categories. One, known as short-acting drugs, includes products like Percocet or Vicodin in which a narcotic is combined with an over-the-counter painkiller. The other category, known as long-acting painkillers, includes drugs like OxyContin, fentanyl and methadone that use a pure narcotic, sometimes in a time-release form.

In its petition, the group asked the agency to limit the drugs' approved use to "severe" pain in patients other than those with cancer.

The petition also urged the agency to put labels on the products that urge doctors to limit the dosages at which the drugs are prescribed to treat noncancer pain and the period of time over which they are used.

Narcotic painkillers are now the most widely prescribed class of drugs in this country; they are also involved in an estimated 15,000 overdose deaths annually, largely involving their abuse.

The use of long-acting painkillers began soaring about two decades ago with the appearance of OxyContin. For years, the drug's manufacturer, Purdue Pharma, and some pain experts contended that such medications could be used safely at extremely high dosages in patients over long periods of time.

However, neither Purdue Pharma nor any drug producer has ever run significant studies to assess the long-term benefits or risks of the medications. And in recent years, studies have linked narcotic painkillers to a variety of dangers, like sleep apnea, sharply reduced hormone production and, in the elderly, increased falls and hip fractures.

Even if the Food and Drug Administration were to adopt the proposed labeling changes, doctors would be free to prescribe drugs "off label" in any way they choose. However, drug companies would face limitations in how they market the products.

http://www.nytimes.com/2012/07/26/business/doctors-petition-fda-for-painkiller-limits.html?src=recg&pagewanted=print

Wednesday, July 18, 2012

Body in Mind — Research into the role of the brain in chronic pain

We want to better facilitate and disseminate credible clinical science research. The motivation lies in our brief as scientists – we reckon that the communication bit of science is the bit that often drags the chain of knowledge development and transfer. We want to communicate our science better. We want to side-step, or perhaps leap-frog, the arduous journey that new discoveries make before they have the opportunity to influence clinical practice. What does Body in Mind want to communicate, exactly? Advances and issues in the clinical sciences as they relate to the role of the brain and mind in chronic pain disorders. There are three subplots we would like to convey, summarised by the three 'C's: complexity, credibility and creativity.
Complexity: We reckon humans are terrifically complex and that embracing this complexity will improve clinical practice.
Credibility: We want to provide information that is evidence-based where evidence exists, that clearly labels speculation as speculation and that is openly and without prejudice, peer-reviewed.
Creativity: We reckon that the chasm that seems to exist between scientists and clinicians is a nuisance. We reckon that if we can bridge this chasm, we will establish a creative space in which scientists and clinicians trust each other and really start to solve some problems. I know, grand hopes. Still, hopes create opportunities, surely.


Chronic Pain Australia | Home

We are dedicated to reducing the social and other barriers to living with chronic pain.We are a group of people who are tired of the way things are for people in pain. You may be feeling quite isolated and 'over it' and feel that no one really understands your experience. You might even feel that people don't believe you. Many people tell us about these experiences. Don't despair, you aren't crazy! And you aren't on your own either. Over the years many volunteers have strengthened us so that we can work towards greater community understanding about chronic pain. 


Chronic Pain Australia receives NO FUNDING from government. This means that we are all volunteers, and together we have achieved a great deal including partnering with the Australian Pain Society and the Faculty of Pain Medicine to develop Australia's First National Pain Strategy. For more on our story, you can go here.




http://www.chronicpainaustralia.org.au/index.php?option=com_content&view=featured&Itemid=101

Are Warnings About the Side Effects of Drugs Making Us Sick? | NeuroTribes

Your doctor doesn't like what's going on with your blood pressure. You've been taking medication for it, but he wants to put you on a new drug, and you're fine with that. Then he leans in close and says in his most reassuring, man-to-man voice, "I should tell you that a small number of my patients have experienced some minor sexual dysfunction on this drug. It's nothing to be ashamed of, and the good news is that this side effect is totally reversible. If you have any 'issues' in the bedroom, don't hesitate to call, and we'll switch you to another type of drug called an ACE inhibitor." OK, you say, you'll keep that in mind.

Three months later, your spouse is on edge. She wants to know if there's anything she can "do" (wink, wink) to reignite the spark in your marriage. She's been checking out websites advertising romantic getaways. No, no, you reassure her, it's not you! It's that new drug the doctor put me on, and I hate it. When you finally make the call, your doctor switches you over to a widely prescribed ACE inhibitor called Ramipril.

"Now, Ramipril is just a great drug," he tells you, "but a very few patients who react badly to it find they develop a persistent cough…" Your throat starts to itch even before you fetch the new prescription. Later in the week, you're telling your buddy at the office that you "must have swallowed wrong" — for the second day in a row. When you type the words ACE inhibitor cough into Google, the text string auto-completes, because so many other people have run the same search, desperately sucking on herbal lozenges between breathless sips of water.

In other words, you're doomed. Cough, cough!

What's going on here? Just medicine-as-usual in a world where valuable drugs have annoying side effects and conscientious health professionals do their best to protect their patients from unpleasant (and potentially litigious) surprises? Sure. But aprovocative new report by Winfried Häuser, Ernil Hansen, and Paul Enck in the journal of the German Medical Association suggests that the side effects of some drugs, and the discomfort of certain medical procedures, may be inadvertently intensified by doctors and nurses trying to keep patients fully informed of the consequences of their medical care. The culprit behind this phenomenon is the nocebo effect.

You can think of the nocebo effect as the evil twin of the placebo effect — the body's healing response to the act of taking a pill or receiving medical care, even if the pill itself is inert. The most familiar example of the placebo effect is what happens in trials of experimental drugs. One group of volunteers is randomly assigned to take the drug in question; another group is assigned to take placebo — a fake drug designed to look just like the real one. Neither the volunteers nor the staff know which group is which. If the drug group improves significantly more than the placebo group, the drug is judged to be effective. This kind of test — thedouble-blind, placebo-controlled trial — has been the gold standard of drug development in medicine for half a century.

In real life, gauging the effectiveness of a new medication is not quite that easy. In 2009, I wrote a widely-circulated article in Wiredmagazine about a mysterious increase in placebo effects in trials in recent years that is making it harder for Big Pharma to bring new drugs to market. I explored some of the reasons that might be happening in the article.

A placebo, you might say, is an ersatz drug that makes you feel better, while a nocebo is a fake drug that makes you feel worse. Of course, in both cases, it's not the pill that's doing the work; it's your own body, responding to the social context in which you take the pill. If a skilled doctor with kindly bedside manner tells you that drug X will reduce the inflammation of a minor injury, it often will — even if the drug itself is nothing but a capsule full of lactose, milk sugar. One of the astonishing things we've discovered about the placebo effect in recent years is how wide a range of ailments can be ameliorated by it, at least temporarily — from chronic pain, to high blood pressure, to inflammation, to depression and anxiety, to sexual dysfunction, to the nausea and vomiting caused by chemotherapy. Perhaps unsurprisingly, it turns out that the nocebo effect is equally capable of making you feel more miserable, in a similarly broad range of ways.

One of the most interesting findings in the new report from Germany is about the underappreciated — and under-studied — role of nocebo effects in clinical trials.

If you tell a group of trial volunteers that they're testing a new drug that may relieve the pain of migraines, a significant number of volunteers will experience pain relief after taking the drug — even if they've been randomly assigned to the placebo group and are receiving nothing but sugar pills. The placebo effect in action.

But here's where it gets interesting. If you tell the volunteers that the side effects of this new medicine may include dry mouth, tingling in the hands and feet, and slight dizziness, some volunteers will experience precisely these side effects — in bothgroups. In fact, some volunteers who are taking nothing but sugar pills will be made so uncomfortable by these symptoms that they will choose to drop out of the trial early.

The relevance of the nocebo effect is not limited to clinical trials. A particularly nasty demonstration of its power can be provided by patients who are being treated for Parkinson's disease with small doses of electrical current delivered to certain structures in the brain. This technique, known as Deep Brain Stimulation (DBS), has been shown to be effective in controlling tremor and other motor issues in patients who are resistant to drugs. But if you tell a DBS patient that the current has been switched off — even though it remains on — their coordination and other motor functions will abruptly decline until you tell them that the juice has been switched on again. Classic nocebo.

The German researchers cite many other examples. In one study, 50 patients with chronic back pain were randomly divided into two groups before a leg flexion test. One group was informed that the test could lead to a slight increase in pain, while the other group was instructed that the test would have no effect. Guess which group reported more pain and was able to perform significantly fewer leg flexions?

Another example from the report: Patients undergoing chemotherapy for cancer treatment who expect these drugs to trigger intense nausea and vomiting suffer far more after receiving the drugs than patients who don't. That's not to say that this nausea is imaginary, purely psychological, or "all in their heads." Like placebo effects, nocebo effects are physiological, not just mental. Researchers like Franklin Miller at the National Institutes of Health and Tor Wager at the University of Colorado are learning that nocebo effects are mediated by neurotransmitters like dopamine, endogenous opioids, and cholecystokinin. Telling a volunteer that the scented Vaseline you're slathering on their arm is a pain-intensifying gel triggers a cascade of chemicals in the body that magnify sensations of discomfort.

How evil can the evil twin of the placebo effect get? Even setting aside anecdotal accounts of evil eyes and "voodoo death" (first reported by a doctor named William Cannon in 1942), nocebo effects can kill, or at least accelerate the progress of disease. In traditional Chinese astrology, some potentially fatal maladies like cancer are associated with certain birth years. A 1993 study of Chinese-Americans who came down with these diseases found that they were more likely to die faster if they were born in an "ill-fated" year associated with the disease — but only if they believed in traditional Chinese astrology. (In these tragic cases, a dose of skepticism could have at least staved off the inevitable for a little while.)

In recent years, the phrase "informed consent" has become a mantra in public health, which is good news for many reasons. But what if the lengthy litanies of side effects we've become accustomed to skimming over — on printouts at the pharmacy, in ads for the latest antidepressants — are self-fulfilling prophecies? What if our well-intentioned desire to prepare patients for the worst increases the probability that the worst will happen?

Even the specific words employed by a doctor can influence the course of a patient's treatment. Some particularly dreadful word choices cited by the German researchers include doctors telling patients:

You must strictly avoid lifting heavy objects — you don't want to end up paralyzed.

You are a high-risk patient.

We're putting you to sleep now. It will soon be all over.

Though the German report focuses on clinical practice and bedside manner, it's hard not to think about the broader implications of nocebo effects in daily life. If you're ever been told twice in one afternoon that you "look a little worn out," you know that it's a miracle if you don't feel utterly exhausted – if not physically ill — by the end of the day. Knowing about nocebo has made me much more careful when making observations about a friend's physical condition.

The German report also points out that nocebo effects deserve much more study. One promising avenue for research might be examining the role of negative messaging in large-scale social phenomena like the apparent increase in food allergies in recent years, or the surge in popularity of gluten-free diets. Having friends with celiac disease and autism, I'm fully aware that some people are truly gluten intolerant, and that banishing the dreaded protein from the menu can avert serious medical problems. But the new report makes me wonder if the flood of anti-gluten "awareness" messages on social networks isn't lengthening the lines for pricey GF pasta, crackers, and doughnuts at my neighborhood Whole Foods Market.The conflict between the need for informed consent in medicine and our bodies' propensity to take social factors into consideration when calculating our own health status is not an easy problem. In recent years, the pendulum has swung so far in the direction of more-bad-news-is-better that it seems almost like heresy to suggest that some of this paternalistic advice may actually be making us sicker.

The new generation of placebo and nocebo research is teaching us that how we feel is highly dependent on the feedback we get from the people around us, particularly from trusted health professionals. The next time I get a headache, you'll forgive me if I don't re-read the label on the aspirin bottle warning me about the possibility of hives, facial swelling, asthma, shock, Reye's Syndrome, nausea, vomiting, severe stomach bleeding, allergic reactions, and distressingly vague "changes in behavior."

I'll just take two and hope for the best.


http://blogs.plos.org/neurotribes/2012/07/16/are-warnings-about-the-side-effects-of-drugs-making-us-sick/

Sunday, July 15, 2012

Pain Medicine News

Pain Medicine News (PMN), is designed to meet the needs of the spectrum of physicians involved in managing pain, including pain specialists, primary care physicians, physiatrists, neurologists, orthopedic surgeons, rheumatologists, oncologists, etc., and is mailed monthly to 50,393 pain-treating physicians that are the highest-prescribers of pain medication in these specialties.

http://www.painmedicinenews.com/Default.aspx

F.D.A. Rejects Mandatory Training in Painkillers for Doctors - NYTimes.com

The Food and Drug Administration, overriding the advice of an expert panel, said Monday that it would not require doctors to have special training before they could prescribe long-acting narcotic painkillers that can lead to addiction.

But the agency said companies that make the drugs, like OxyContin, fentanyl and methadone, would be required to underwrite the cost of voluntary programs aimed at teaching doctors how to best use them.

The F.D.A. announcement came after several years of deliberations by the agency into the growing problem of prescription painkiller abuse and misuse. In 2010, a panel of outside experts assembled by the F.D.A. overwhelmingly rejected the agency's proposal that physician training be voluntary.

Instead, that panel said that mandatory training was essential both to reduce the abuse of strong painkillers, or opioids and to make sure that pain patients were treated appropriately with them.

In introducing the plan on Monday, both Dr. Margaret A. Hamburg, the F.D.A. commissioner, and R. Gil Kerlikowske, President Obama's top drug policy adviser, said they were hopeful that Congress would eventually enact mandatory physician training.

But the Obama administration has yet to draft legislation, despite voicing support for more than a year.

Major doctors groups like the American Medical Association have fought the idea of mandatory training, saying that the programs would be burdensome and could reduce the number of physicians who treat pain patients.

Over the last decade, overdose deaths related to the abuse and misuse of long-acting narcotics have reached epidemic proportions.

There are also growing concerns that long-term use of the drugs can cause a variety of problems, such as sharply reduced hormone production, sleep apnea and increased falls and fractures in people over 70.

Dr. Scott M. Fishman, a pain specialist, said he believed that the public health issues surrounding opioid use had reached a point at which doctor training was essential.

"The problem of prescription drug abuse has become so severe, I believe that the time has come to make that training mandatory," said Dr. Fishman, a professor at the University of California, Davis.

Under the F.D.A. plan announced Monday, drug makers will underwrite the development of physician education programs, but the companies will not control their content, F.D.A. officials said.

Instead, groups that specialize in training programs for doctors will create the courses, which are expected to last two to three hours, the agency said.

The plan also calls for patients to receive one-page handouts about the benefits and risks of opioid use.

Dr. Hamburg, the head of the F.D.A., said the agency hoped that about 60 percent of the country's doctors who prescribe long-acting opioids would take the educational courses within three years after the programs start.

"We are embarking on a very positive course and as physicians start to receive education," they will respond, Dr. Hamburg said.

http://www.nytimes.com/2012/07/10/health/fda-rejects-mandatory-training-in-painkillers-for-doctors.html?src=recg&pagewanted=print

Wednesday, July 11, 2012

Novel Blood Treatment Lures Athletes in Pain to Germany - NYTimes.com

DÜSSELDORF, Germany — The medical treatment for Lindsey Berg's arthritic left knee has not been approved by the Food and Drug Administration, and neither her professional volleyball team in Italy nor the United States Olympic team would help with the cost. But for Berg, a gold medal hopeful, the chance to dull the chronic pain was worth the money, and the risk.

So between the end of her professional season and the start of Olympic practices in California, Berg stopped at the office of Dr. Peter Wehling on the bank of the Rhine River. "I've been struggling with knee pain for the last four years and just continuing to play on it," said Berg, 31, who had tried surgery and cortisone injections to little avail.

After examining her, Wehling and his team drew syringes of her blood. First they incubated it. Then they spun it in a centrifuge. The blood cells produce proteins that reduce inflammation and stimulate cellular growth; sometimes additional anti-inflammatory proteins are added to the solution. Finally, Wehling injected the orange serum into Berg's knee.

The price came to 6,000 euros, or about $7,400, out of her own pocket, but with the Olympics in London coming up, any treatment that might make her knee better was worth it. "It's your body and your money because they're not paying for it," she said with cheerful resignation, on the fourth day of her treatment.

Wehling's practice has become almost a pilgrimage site for athletes trying to prolong careers that have tested the limits of their bodies. It has also been the subject of no small amount of speculation after word leaked last year that the Los Angeles Lakers star Kobe Bryant had flown to Düsseldorf for the treatments. Alex Rodriguez of the Yankees traveled there as well. After the N.B.A. season ended, Lakers center Andrew Bynum, Bryant's teammate, said he, too, would try it.

Commentators wanted to know if there was something fishy that required Bryant to go abroad for medical treatment. As his scoring average increased and the aging star seemed rejuvenated, the interest in the trips to Germany and the unusual treatment grew.

To answer the most common questions: Wehling's practice is not at the end of a dark alley but in a modern building south of the city's old town; it is brightly rather than dimly lighted, with orange floors and a water cooler in the waiting room; and Wehling seems more like a true believer in his Regenokine therapy than a snake-oil salesman. He said he was careful not to use any substances banned by athletic governing bodies.

Biologic medicine is a rapidly growing field. Wehling's Regenokine treatment might sound similar to another blood-spinning treatment, known as platelet-rich plasma, or P.R.P., that has gained popularity in the United States in recent years. In that procedure, the goal is to produce a high concentration of platelet cells, which are believed to speed the healing process. Wehling said his treatment differed from P.R.P. because he heats the blood before it is spun to increase the concentration of anti-inflammatory proteins, rather than the platelets, in his cell-free solution.

The idea is not just to focus on mechanical problems in the joints or lower back but to treat inflammation as a cause of tissue damage as well as a symptom.

"The potential of biology to treat orthopedic problems is high because it has only been developed a little," Wehling said in an interview.

"It has to be embedded in a good concept more broadly," he added, emphasizing that sleep, diet and conditioning are among the important components to go with the injections. "There's no such thing as the one therapy that fixes everything."

On a recent morning he treated not only Berg but also a basketball player, a golfer, a Hollywood executive and a former martial artist.

"The results were incredible," Vijay Singh, the world's former No. 1 golfer and a patient of Wehling's, said in a telephone interview. "It's like somebody just put oil all over your body. It lubes you up, and you're able to move more freely, especially pain free."

The question is how effective the treatment will prove in the long run.

Dr. Freddie Fu, a professor of orthopedic surgery at the University of Pittsburgh, has been critical of many such treatments, including P.R.P. He was slightly more optimistic about Wehling's approach.

"The gimmick is, it's your own body, it must be safe," Fu said. "There has been some impressive research done already, and there is a good scientific fundament to do more research.

"However, before the F.D.A. approves, more high-quality independent trials have to be done in order to prove the effectiveness."

Recent patients speak glowingly of the doctor as well as his therapy.

"When you come here and are skeptical and all your pain disappears, it makes you all the more devoted to the science of it," said Tim Shaheen, from Los Angeles. "What about people on assembly lines with terrible knees and terrible backs? This would be a lifesaver for that in quality of life."

The therapy generally lasts five days, starting with an evaluation and, if the patient decides to go ahead, drawing the blood.

"As much blood as they took the first day, I didn't think I'd have any left," said Wes Short Jr., a professional golfer from Austin, Tex. It was his first trip to Germany, he said, indeed his first to a non-English-speaking country, and he still marveled at the fact that most of the taxis were Mercedeses.

Short lay on his stomach, his green short-sleeve shirt hiked up. Wehling had just injected several syringes of serum into the small of his back. Afterward the doctor left half a dozen acupuncture needles quivering in Short's back.

The fact that Wehling had treated Pope John Paul II made a strong impression on Short. "I'm sure he doesn't trust just anybody," said Short, who hoped to start playing again if the treatment worked.

Wehling's book "The End of Pain" begins with a "Da Vinci Code"-style trip to the Vatican and, escorted by the Swiss Guard, into John Paul II's private chamber. "The hard marble floors echoed with emptiness," Wehling wrote. But why, he asked, had the pope chosen his treatment? "Because your treatment comes from God," the pope said, referring, Wehling wrote, to the fact that it comes from the body.

Wehling comes from an old Rhineland family. His great-uncle was the archbishop of Cologne, and as a boy he met the future Pope Benedict XVI, Joseph Ratzinger. A father of two, Wehling plays keyboard in two bands, one jazz and one blues, giving off the vibe of a goofy-cool uncle, a little too enthusiastic to be completely hip.

"He's very honest," said Jeff Kwatinetz, president of the production company Prospect Park, who traveled from Los Angeles to receive the treatment on both shoulders. He was as impressed with Wehling's bedside manner as the mobility he had regained in his joints. "He hopes it can work, thinks it can work, but he's not making any promises."

Wehling manages to buzz through his clinic at high speed yet somehow make each patient feel as though he has all the time in the world for him or her. When talking to Wehling, the term "exciting," is often used — the research, the possibilities. There are two offices, one in New York and one in Los Angeles, licensed to provide a similar treatment, though they cannot advertise because of the lack of F.D.A. approval.

"When you're one of the progenitors of a new way of thinking, you really want to have it thrive," said Chris Evans, the Müller professor of orthopedic surgery at Harvard Medical School, who wrote the introduction to Wehling's book and serves unpaid on the supervisory board of the company Wehling founded. He is developing an idea that came to him when he was a young resident in neurophysiology and orthopedics, Dr. Evans said, and "now that he's middle-aged he wants to see that it's out there and that it works."

Saturday, July 07, 2012

After Delay, OxyContin’s Use in Young Is Under Study - NYTimes.com

To learn how best to prescribe powerful drugs to children, Congress passed a law in the 1990s that rewarded drug makers for conducting clinical studies involving children. Among the incentives for cooperating companies was a possible six-month extension of protection from generic competition after a drug's patent expired.

More than a decade ago, federal regulators asked the producer of OxyContin, a widely abused narcotic painkiller, to run such a trial under the law. The producer, Purdue Pharma, started a study of children but dropped it in 2004, citing limited financial resources. Now, with OxyContin's patent set to expire in 2013, the company has begun another study of young patients — opening the possibility for a patent extension for Purdue, worth hundreds of millions of dollars.

The company's long delay in complying with the Food and Drug Administration's request rankles critics, who say it is coming far too late for many children. Since the time that the F.D.A. asked Purdue to conduct the research, doctors have prescribed OxyContin to tens of thousands of children and teenagers without the benefit of study data to guide them.

"It looks to me like a raw, crass, last-gasp exploitation of a drug that has been synonymous with misuse, abuse and harm to patients," said Dr. Arthur Caplan, the head of the division of medical ethics at NYU Langone Medical Center.

A spokesman for Purdue, which is based in Stamford, Conn., said that the company decided in 2004 to redirect the money it was spending on a pediatric trial into an effort to develop a version of OxyContin that was more resistant to being abused.

"We reinitiated the remaining pediatric trials once we had the necessary resources to continue them," said that spokesman, James W. Heins. "These trials are challenging to conduct and can take years to complete."

In 2004, the year Purdue Pharma abandoned the trial, sales of OxyContin reached $1.7 billion, according to IMS Health, a consulting firm. Over the last decade, sales of the painkiller have exceeded $15 billion.

No one questions that OxyContin, a time-release version of a narcotic drug or "opioid" called oxycodone, can benefit some younger patients suffering severe pain from cancer or conditions like sickle cell anemia. Some experts say the study will provide useful data to guide the drug's use.

But other experts worry that little is known about OxyContin's long-term risks in adults, much less children.

For example, opioids like OxyContin have been shown to reduce the production of sexual hormones in both men and women, leading to extreme lethargy and lack of drive.

"Opioids have endocrinological effects and therefore potential developmental complications are a concern," said Dr. C. Richard Chapman, the former head of the Pain Research Center at the University of Utah. "It just doesn't make sense."

In 1997, Congress passed the Best Pharmaceuticals for Children Act, the statute that created the incentive for drug makers to test the products in young patients. Not long after the bill's passage, the Food and Drug Administration formally requested that Purdue Pharma conduct three studies of oxycodone, OxyContin's active ingredient, said the company spokesman, Mr. Heins.

In written responses to questions, Mr. Heins said that the company completed two of those studies, both of which involved oxycodone in liquid form, the way a drug might be administered in a hospital using an injection or through an intravenous drip. But the third study requested by the F.D.A. — a pediatric trial of OxyContin itself, a time-release pill form of oxycodone — was not conducted.

Mr. Heins said the company abandoned the trial in 2004 after enrolling just a few patients. "It had to be discontinued because of a lack of resources," Mr. Heins wrote.

Mr. Heins added the company focused its spending on the development of a more abuse-resistant form of OxyContin. Purdue Pharma has since patented that version of the drug and is now marketing it.

Pediatric drug studies can cost millions of dollars to conduct.

A spokeswoman for the F.D.A., Karen Riley, declined as a matter of policy to discuss the agency's interactions with Purdue Pharma because it involved business confidential information.

In 2009, about a decade after the F.D.A.'s original request, Purdue Pharma assembled a panel of experts to discuss how to best proceed with the pediatric trial of OxyContin, Mr. Heins said. New talks with the F.D.A. followed and an agreement was reached in 2010 on a trial design, he added.

The company's pediatric study drew public attention this week when The Daily, an online publication, wrote an article about it.

Dr. Nathaniel P. Katz, a pain management expert, said that over the last decade, the F.D.A. had changed the type of information it seeks from makers of narcotic painkillers who run pediatric trials. Initially, he said, the agency wanted studies similar to traditional trials in which some patients were put on the drug being studied and other patients received a placebo like a sugar pill.

"Where are you going to find parents willing to take the risk that their child will be put on a placebo?" Dr. Katz said.

The study that Purdue Pharma is currently conducting is not a placebo trial. Instead, it involves about 150 patients from 6 to 16 years of age who are already on opioid painkillers. In the study, which is expected to be completed next year, those patients will get OxyContin for up to six months.

Senator Richard Blumenthal, a Democrat of Connecticut who investigated Purdue Pharma while attorney general of that state, said that while the company might benefit from the pediatric testing law, its delay in running the OxyContin trial did not appear to reflect the statute's spirit.

"If a drug is going to be used on children, tests to ascertain its safety should be run as early as possible," he said.


Sunday, July 01, 2012

Blaming the Brain for Chronic Back Pain - ScienceNOW

The vast majority of adults have had a sore back at some point in their lives. If they're lucky, the pain subsides after a few days or weeks. But for some, whose initial injuries appear no different than the fortunate ones, back pain lasts for years. Now, researchers have discovered a difference in brain scans between the two groups of patients that appears early in the course of the pain. The finding could lead to not only ways of identifying patients who are the most at risk for long-term pain but to new treatments or preventions for chronic pain.

"This is the very first time we can say that if we have two subjects who have the same type of injury for the same amount of time, we can predict who will become a chronic pain patient versus who will not," says neuroscientist Vania Apkarian of Northwestern University, Chicago, who led the new work.

Over the past 2 decades, Apkarian's lab has run many studies comparing the brains of patients with chronic back pain with those of healthy people, finding differences in brain anatomy or the function of certain regions. But the study designs made it hard to sort out which brain changes were consequences of the chronic pain—or the patients' painkillers or altered lifestyles—versus those that drove the pain's chronic nature.

Apkarian and colleagues have now tracked the brains of back pain patients over time rather than comparing single neural snapshots. His team began with 39 people who had experienced moderate back pain—a five or six on a self-described scale of 10—for 1 to 4 months. Over the next year, the team scanned the patients' brains four times and followed their pain. By year's end, 20 of the patients had recovered, while 19 continued to hurt, meeting the criteria for chronic pain.

The scientists then looked at a number of brain characteristics, including the amount of communication between two areas of the brain previously seen to have altered activity in back pain patients: the insula and the nucleus accumbens. These regions are involved in emotional responses to a person's environment and in how the brain learns. Not only did they measure more communication between the two areas in chronic back pain patients than in those whose pain subsided, but the increased crosstalk could be seen as far back as the start of the study, suggesting that it could have predicted which patients would suffer the whole year. But further work will need to confirm that the scans have predictive value.

The results, published online today in Nature Neuroscience, could be used to pinpoint patients who are at the highest risk for chronic pain, says Apkarian. And drugs could be developed to dampen the communication between the brain areas in such patients to treat or prevent chronic pain.

"Our interpretation of the results is that how these areas of the brain engage with the injury then dictates how the rest of the brain is going to reorganize," says Apkarian. It underscores that brain regions involved in learning and emotions are important in the development of chronic pain, he says, not just brain regions directly responsible for sensing pain.

"This is a transformative piece of work," says neurologist David Borsook of Harvard University, who was not involved in the study. "Finding that these changes are predictive is very exciting."

Borsook says more research is needed to completely sort out what makes pain chronic; the new finding is likely only one piece of the puzzle. "We're still not sure when acute pain transforms to chronic pain," he says. "We use these arbitrary time points." And the results need to be repeated with different patient populations and study designs to gain traction within the field, he says. But the new study is a step on the way to having quantitative ways of defining pain by using scans, rather than relying on descriptions of the pain from patients.

"This is a fantastic thing for the field of pain imaging," Borsook says, "and I have no doubt that this same data set holds other findings about chronic pain that we will learn about in the near future."


http://news.sciencemag.org/sciencenow/2012/07/blaming-the-brain-for-chronic-ba.html?ref=hp