Sunday, January 26, 2014
Toronto—One-third of results from registered clinical trials of neuropathic pain treatments are not readily available, according to an extensive survey of neuropathic pain literature.
According to Michael Rowbotham, MD, scientific director of the California Pacific Medical Center Research Institute in San Francisco, the unavailability of such a swath of trial results, compounded with selective publication bias, carry significant ethical, research and clinical implications.
"One problem is that the aggregating of these data tends to inflate treatment effect sizes," said Dr. Rowbotham. "If you overestimate the effect size, you really harm everyone. Physicians and patients get inappropriately high-efficacy expectations; future trials are designed to be underpowered because they're looking for a bigger effect than they really should be and from an ethical perspective, not sharing the findings wastes the contributions of patients who have entered clinical trials and agreed to the possibility of experiencing unknown risks."
Congress requires clinical trials conducted in the United States to be registered on clinicaltrials.gov and that some trial results be posted on the website within one year of a study's completion. However, previous research has found only 8% to 10% of all completed trials have accompanying findings on the registry (JAMA 2012;307:651-653).
To capture a snapshot of neuropathic pain–related registered clinical trials and trial result availability, Dr. Rowbotham and several of his colleagues created the Repository of Registered Analgesic Clinical Trials (RReACT), a project of the Analgesic Clinical Trial Translations, Innovations, Opportunities and Networks (ACTTION).
Their most recent research was a survey of the results from postherpetic neuralgia (PHN), fibromyalgia (FM) and diabetic peripheral neuropathy (DPN) trials registered on clinicaltrials.gov. They looked at the registry's website, as well as peer-reviewed journals, conference abstracts and press releases. The latter are referred to as "the grey literature."
Their results, which can be found at www.acttion.org, showed 373 registered studies on the three neuropathic pain conditions as of December 2011. In all, 184 trials were completed before December 2010, and therefore many should have had findings posted, as per the Congressional one-year deadline requirement.
However, the researchers' comprehensive search yielded no findings for 24% of the DPN studies, 25% of the FM trials and 33% of the PHN studies completed before December 2010.
The proportion of complete and incomplete trials that had results available in any format ranged from 63% to 68%. Furthermore, only 39% to 44% of all findings were published in peer-reviewed journals.
"If you work really hard, use sophisticated search strategies and look at all public websites including the grey literature, you can get results from about two-thirds of studies," Dr. Rowbotham said.
The grey literature is not a reliable source for findings, given that results are not peer-reviewed, Dr. Rowbotham said, adding that there are other problems with accessing these findings.
"One of the websites we relied on as a source for this analysis, disappeared," said Dr. Rowbotham. "It took with it results from hundreds of trials, several of which we couldn't find anywhere else."
According to Dr. Rowbotham, analyses and reviews of published evidence need to consider not only the absence of up to one-third of findings, but also the documented problem of publication bias.
Publication bias received widespread attention when a 2008 study in The New England Journal of Medicine found that of 74 large, multicenter, Phase III trials of 13 antidepressant drugs approved by the FDA, half were not published in the peer-reviewed literature, and findings that were published tended to be positive (N Engl J Med 2008;358:252-260).
"Not only were positive results more likely to be published, but studies that were not positive, in the researchers' evaluation, were often published in a way that conveyed a positive outcome," Dr. Rowbotham told attendees at the 4th International Congress on Neuropathic Pain. "One way to do this is to promote a positive secondary outcome and devote lots of text in the paper as if it were the most important outcome."
Although it is possible that some of the neuropathic pain trial findings that were found to be unavailable in the RReACT analysis may have been negative, Dr. Rowbotham's team did not set out to identify why results were not available. A less insidious explanation is the "file drawer problem," he said.
"Some studies seem to get published and others just languish, waiting for that final review and edit, or for time to start writing the manuscript," Dr. Rowbotham speculated.
Despite the worrisome RReACT findings, there are an increasing number of efforts by a spectrum of health care stakeholders to improve the accessibility of clinical trial findings, according to Swaroop Vedula, MD, PhD, postdoctoral fellow at Johns Hopkins University in Baltimore.
"We have a long way to go before trial protocols and findings are reported completely and transparently," said Dr. Vedula, who has studied the reporting of gabapentin trials and is not involved in RReACT. "However, there are several important initiatives, including a big push lately for open access to trial data, that are changing our understanding of the accuracy of clinical trial reporting and making clinical trial data and documents publicly available."
Saturday, January 25, 2014
The International Association for the Study of Pain will hold its 15th World Congress on Pain October 6-11, 2014, in Buenos Aires, Argentina! The Congress will attract more than 6,000 pain specialists from all over the world who will converge on Buenos Aires and present the most up-to-date information on the field of pain, from laboratory science to clinical diagnosis, management, and prevention.
The Buenos Aires Scientific Program Committee will organize a program to include plenary sessions, topical workshops, refresher courses, and poster sessions covering every aspect of acute and chronic pain from basic science to clinical practice. We hope to see you there!
IASP is pleased to announce the program of Distinguished Lectures, Refresher Courses, Plenary Lectures, Topical Workshops, and Satellite Symposia for the Congress. Browse the program today to find topics of interest to you.
Tuesday, January 14, 2014
America spends more than $80 billion a year on back pain treatments. But many specialists say less treatment is usually more effective.
In fact, there's evidence that many standard treatments for back pain — surgery, spinal injections and painkillers — are often ineffective and can even worsen and prolong the problem.
Dr. Jerome Groopman agrees with that premise. He suffered back pain for almost 20 years. He was a young marathon runner 32 years ago when back pain struck out of the blue.
"I couldn't run. It was difficult to sleep," he says. "I wasn't confined to bed, but I was hobbling around."
Groopman, a Harvard cancer specialist who writes about medicine for The New Yorker, wanted the problem fixed — right away. So he found a surgeon who removed a damaged disc, the jellylike cushioning between each vertebra.
The surgery didn't fix his pain.
Then, one day during brunch at a friend's house, something happened that altered the course of his life.
"I stood up from a chair and just had an explosive electric shock through my lower back," he remembers. "Basically, I fell to the floor and couldn't get up."
His previous pain was severe. But this was over the top. Groopman could hardly move.
"I was so desperate after almost three weeks that I found a neurosurgeon and orthopedist who said, 'You have spinal instability. We'll fuse you, and in three weeks you'll be playing football.' "
In a spinal fusion, surgeons weld together adjacent vertebrae with a bone graft. It's anincreasingly common operation.
But for Groopman, more surgery made things worse.
"I woke up from the surgery in excruciating pain, and basically could hardly move my legs," he says. "And I remember the orthopedic surgeon coming by and saying, 'Well, I don't know why you're having so much trouble. ... But, you know, if it doesn't get better in a few weeks we could reoperate.' "
Some research suggests that 1 in 5 patients who have surgery for back pain end up having more surgery. For some, like Jerry Groopman, it doesn't help at all.
There's "good reason to think that we are overprescribing painkillers, overprescribing injections, overprescribing back surgery," according to Dr. Richard Deyo. He is an authority on evidence-based medicine at Oregon Health Sciences University who has studied treatment of back pain.
One reason invasive treatments for back pain have been rising in recent years, Deyo says, is the ready availability of MRI scans. These detailed, color-coded pictures that can show a cross-section of the spine are a technological tour de force. But they can be dangerously misleading.
"Seeing is believing," Deyo says. "And gosh! We can actually see degenerated discs, we can see bulging discs. We can see all kinds of things that are alarming."
That is, they look alarming. But they're most likely not the cause of the pain.
Lots of people who are pain-free actually have terrible-looking MRIs. And among those who have MRI abnormalities and pain, many specialists question whether the abnormality is really the cause of the pain, and whether fixing it can make the pain go away.
Surgery can help for certain conditions, such as a herniated or bulging disc with leg pain called sciatica. But most age-related back pain usually can't be fixed with surgery.
Research is showing that the pain often has nothing to do with the mechanics of the spine, but with the way the nervous system is behaving, according to Dr. James Rainvilleof New England Baptist Hospital in Boston.
"It's a change in the way the sensory system is processing information," says Rainville, who is a physiatrist, or specialist in rehabilitation medicine. "Normal sensations of touch, sensations produced by movements, are translated by the nervous system into a pain message. That process is what drives people completely crazy who have back pain, because so many things produce discomfort."
This is a different way of thinking about pain. Normally pain is an alarm bell that says, "Stop what you're doing right now or you may hurt yourself!" But for many people, that pain is a false signal. It's not about looming danger; it's actually caused by hypersensitive nerves.
Rainville says that about 25 percent of patients with acute back trouble get stuck in an endless loop of pain. He thinks this chronic back pain is often due to persistent hypersensitivity of the nervous system.
Genetics may help explain why back pain becomes chronic for that 25 percent. But whatever the underlying cause, Rainville and others have discovered that many of them can learn to ignore their pain.
That process requires around six weeks of regular visits to a back pain "boot camp," where specially trained therapists gradually increase the intensity of exercises designed not only to increase the strength and flexibility of the back, but also to teach patients that it's OK to move normally again.
Janet Wertheimer is a 61-year-old Massachusetts woman who recently completed Rainville's boot camp. She has had severe back pain on and off for 10 years.
One recent morning, therapist Lisa Childs put Wertheimer through her paces, starting with a rotary torso machine that required her to twist her back this way and that against the resistance of a stack of iron plates.
Next she moved to a back extension device. Wertheimer arched her back against the weight stack — by this point in her rehabilitation, 100 pounds of weight. It's something most people with chronic back pain couldn't imagine doing.
"Do you feel like you could do 5 pounds more or 10 pounds?" Childs asks.
"You can try 10 and I'll see what happens," Wertheimer says.
Wertheimer has a sudden twinge in her back. But Childs, who's trained to evaluate these things, says it's OK. Wertheimer is building strength. And along the way, she's learning not to be afraid. "It's learning not to fear the pain, learning that you can live with pain," Wertheimer says. "Understand what that pain is, but then put it aside."
Most patients in Rainville's boot camp and similar programs find that the pain eventually lessens over a few months. Sometimes it even goes away.
For years after his spinal fusion, Groopman was never without back pain. He tried a long list of things without success. Then a friend suggested that he see Rainville.
Given his long search for relief, Groopman was skeptical. But he decided to give Rainville's boot camp a try.
"He was really tough," Groopman recalls. "He said to me, 'You are worshiping the volcano god of pain!' And I thought: 'What is this about?' "
Rainville explains: "In primitive cultures, if you lived near a volcano and the volcano started smoking and looking like something was going to happen, well, it was obvious[ly] because gods were mad at you. And you'd start doing silly things — sacrificing chickens or goats or whatever, thinking that that would appease the gods."
In a strange way, Rainville says, people with chronic back pain do something very similar. They sacrifice parts of their life — playing golf or softball, running, picking up bags of groceries or grandchildren. Patients get so afraid of pain, they do anything to avoid it.
"They keep putting things onto this altar, thinking that's going to change the situation," Rainville says.
But it usually doesn't work. Instead, they get more paranoid about any twinge of pain, and all the while they lose strength and flexibility.
Eventually that message sank in with the skeptical Dr. Groopman. "It took about two months for me to really buy in that this was the way to go," he says. "Just let it go. Don't pay attention to it. ... And after about nine months, I was basically without any back pain."
It doesn't work that well for everyone. Janet Wertheimer still has some back pain. But she says after graduating from boot camp she can pretty much do anything she wants to — ski, go on mountain hikes, walk her dogs.
And the pain? Most of the time, she says, she blocks it out and moves on.
Monday, January 13, 2014
The Brain: Adaptation and Maladaptation in Chronic Pain, June 15-20, 2014, Keystone Resort, Keystone, Colorado, USA
Monday, January 06, 2014
In her new book — A Nation in Pain: Healing Our Biggest Health Problem — author Judy Foreman provides a deeply researched account of today's chronic pain crisis and reasons behind it, and she discusses some solutions that could be within reach. Far more than just a symptom, Foreman explains, chronic pain can be a disease in its own right, and the failure to manage pain better in the U.S. and other countries worldwide may be tantamount to torture.
A great many (perhaps, too many) books have been written on the subject of pain; all are well-intentioned and often they are self-published. While some of the books are of interest, most appear to be riddled with personal opinion, biased perspectives, and/or misinformation rather than being guided by facts and solid evidence. As a journalist and investigative health reporter, Foreman has done a noteworthy job of crafting easy-to-read text that also is excellently documented with enough citations of her evidentiary sources to satisfy even the most skeptical readers — which is quite rare for a book intended for both lay and professional audiences, as is A Nation in Pain.
The 464 page book, published by Oxford University Press, is ambitious in scope, covering in a mere 14 chapters subjects ranging from the nature of pain to genetic, age, gender, immune system, and mind-body influences. Foreman also examines various traditional, newly discovered, and alternative therapies for chronic pain.
She says that her research for A Nation in Pain spanned 5 years, during which time Foreman consulted a library of books and hundreds of scientific papers on pain. She also interviewed nearly 200 scientists and physicians, as well as countless patients, a few lawyers, and a handful of government officials. [Full disclosure: This writer was one of those persons consulted, and we can attest to the depth and relentless probing of her inquiries.]
A most appealing approach of the book is that it is simultaneously a textbook providing research insights and hard evidence, an investigative report replete with stories of affected patients and their families, and a personal memoir relating Foreman's own experiences with chronic pain and its treatment. Certainly, this juggling was no easy task, but the genre makes for fast-paced, informative reading while captivating even a casual reader.
Overall, Foreman suggests that there is an appalling mismatch between what people in pain need and what healthcare providers know about pain and its treatment — chronic pain in particular. She found that physicians in the U.S. typically receive only about 9 hours of education specifically on pain during 4 years of medical school — even veterinarians are better educated on pain management.
Systematic failure is equally evident at the federal government level; for example, in 2012 the U.S. National Institutes of Health spent only about 1% of its vast $30.8 billion budget on pain research, Foreman states, despite the fact that chronic pain was (and still is) a bigger problem than heart disease, cancer, and diabetes combined. At the same time, chronic pain in the U.S. conservatively costs as much as $650 billion per year in direct medical costs and lost productivity. Shamefully, there is no National Institute of Pain; yet, there are other Institutes addressing diverse health conditions that are important, but affect far fewer citizens and with less burden on the economy.
One of the more startling chapters in A Nation in Pain discusses the mismanagement of pain in pediatrics. Among other revelations, Foreman discloses how as recently as the mid-1980s in the U.S. healthcare professionals believed that young children, especially newborns and infants, seldom needed medication for pain relief and tolerated discomfort well. She recounts the particularly disturbing story of a newborn boy who was subjected to open-heart surgery without anesthesia — a practice that apparently was commonplace at the time, but somewhat of a dark secret known only among medical insiders. In general, management of pain in children of all ages has been deficient worldwide, as Foreman reveals in an examination of the research evidence.
Foreman devotes 2 chapters to the destructive "Opioid Wars," which have led to a misguided demonization of prescription opioid analgesics. Her discussion of this highly controversial topic is among the most fairly-balanced and evidence-based that we have seen. She observes that there are 2 separate public health "emergencies," sometimes called "epidemics": (a) undertreated pain influenced by some degree of limited access to opioids, and (b) the abuse of opioid analgesics for illegal or nonmedical purposes. She stresses, "whether the term 'epidemic' truly applies here is debatable."
Foreman recognizes that there are many sides to the ongoing debate and relatively little hard evidence one way or the other. As she states, "The complex truth is that opioids, especially opioids for long-term use in chronic non-cancer pain, are probably both under-prescribed for some patients and overprescribed for others." Opioids are not a solution for all patients or all types of severe pain, she acknowledges, and at best the pain relief they afford is only partial. She accordingly emphasizes:
"Opioids, in other words, may be necessary, but they are rarely sufficient. What I am saying is that government drug policy seems to be lopsided, politicized, stacked against legitimate pain patients, and fueled by public hysteria over abuse of prescription pain relievers. That hysteria, in turn, is fueled by often-misleading media coverage."
Those few sentences say a great deal about what has gone awry with concerns about opioid analgesics today. In support of those statements, Foreman laces her discussion with references to relevant research studies, while also distinguishing between good- versus poor-quality evidence — an objectively analytical perspective that is missing in most other books and articles on the subject.
As Foreman observes, the controversy over prescription analgesics is a "highly emotional struggle in which much of the 'debate' is driven not by scientific facts but by dueling anecdotes of horror." She aptly denounces a misguided popular press, prejudiced bureaucrats, and a small cadre of fear-mongering medical professionals for trying to foist a negatively slanted view of opioid pain relievers on the public as well as on the healthcare community at large. In balance, Foreman also tells how over-exuberant marketing by drug manufacturers has contributed to problematic analgesic prescribing and use.
Throughout the book various therapeutic approaches for managing chronic pain are discussed, including new developments still in preclinical or clinical trial stages. Additionally, a whole chapter is devoted to marijuana ("The Weed America Loves to Hate") and another focuses on exercise ("The Real Magic Bullet"). A range of CAM (Complementary & Alternative Medicine) therapies also are covered, with balanced discussions of pro and con research evidence for each.
Challenges of effective chronic-pain management are complex, with many obstacles to overcome on the path to finding practical solutions. As the diverse stories of patients with pain in the book demonstrate, pain often cannot be extinguished altogether; yet, it almost always can be better managed and patients can live more fulfilling lives. Foreman offers some suggestions for action — such as expanded pain education in medical schools, reforms of federal policies across the board, and increased funding for pain research — but it would require a separate book to do justice to such proposals. Meanwhile, for healthcare providers, researchers, policy makers, and patients and their loved ones, A Nation in Painis highly recommended reading.
Here is ordering information…..
A Nation in Pain: Healing Our Biggest Health Problem
Judy Foreman; Oxford University Press; ISBN-10: 0199837201 | ISBN-13: 978-0199837205
Release Date: January 29, 2014
Hardcover (464 pages); List Price $29.95 USD (discounts often available).
See video trailer here: http://judyforeman.com/books/a-nation-in-pain/trailer/
Chronic widespread pain, including fibromyalgia: a pathway for care developed by the British Pain Society