PharmaLive: Questions and answers on recommendation for the refusal of a change to the marketing authorisation for Cymbalta/Xeristar

On 23 October 2008, the Committee for Medicinal Products for Human Use (CHMP) adopted a negative opinion, recommending the refusal of a change to the marketing authorisation for the medicinal product Cymbalta/Xeristar 30 mg and 60 mg gastroresistant capsules. The change concerned an extension of indication to add the treatment of fibromyalgia. The companies that applied for authorisation are Eli Lilly Nederland B.V. (for Cymbalta) and Boehringer Ingelheim International GmbH (for Xeristar). They may request a re-examination of the opinion within 15 days of receipt of notification of this negative opinion.

What was Cymbalta/Xeristar expected to be used for?

Cymbalta/Xeristar was also expected to be used to treat adults with fibromyalgia, a disease causing long-lasting, widespread pain and painful responses to touch. Fibromyalgia can also cause other symptoms such as tenderness, stiffness, tiredness, anxiety and changes in how the patient sleeps, feels and thinks. The cause of fibromyalgia is not known. Cymbalta/Xeristar was expected to be used in fibromyalgia patients with or without depression.

How is Cymbalta/Xeristar expected to work?

The active substance in Cymbalta/Xeristar, duloxetine, is a serotonin-noradrenaline re-uptake inhibitor. It works by preventing the neurotransmitters 5-hydroxytryptamine (also called serotonin) and noradrenaline from being taken back up into nerve cells in the brain and spinal cord.

Neurotransmitters are chemicals that allow nerve cells to communicate with one another. By blocking their re-uptake, duloxetine increases the amount of these neurotransmitters in the spaces between these nerve cells, increasing the level of communication between the cells.

Since these neurotransmitters are thought to be involved in fibromyalgia, blocking their re-uptake into nerve cells is expected to improve the symptoms of the disease.

What documentation was presented to support this application?

The results of five studies involving a total of 1,718 adults with fibromyalgia were presented to the CHMP to support the application. Four of the studies were short-term, lasting between three and six months, and comparing Cymbalta/Xeristar with placebo (a dummy treatment) in a total of 1,411 patients. The fifth, a long-term study, compared the effects of two doses of Cymbalta/Xeristar over a year in 307 patients.

In all of the studies, the main measures of effectiveness were based on changes in the patients' symptoms, particularly pain levels, and their overall state of health. These were measured using standard scales and questionnaires.

What were the major concerns that led the CHMP to recommend the refusal of the change to the marketing authorisation?

The CHMP was concerned that the effectiveness of Cymbalta/Xeristar in treating fibromyalgia had not been shown sufficiently. In the short-term studies, the CHMP considered that the effect of Cymbalta/Xeristar was too small to be relevant for patients: there was no clear demonstration of improvement in symptoms, and the modest effects of Cymbalta/Xeristar could be due to the medicine's effect of improving the patients' mood. The CHMP also concluded that the long-term study was insufficient to show the effectiveness of the medicine and that a long-term study comparing Cymbalta/Xeristar with placebo would be needed.

At that point in time, the CHMP was of the opinion that the benefits of Cymbalta/Xeristar in the treatment of fibromyalgia did not outweigh its risks. Hence, the CHMP recommended that the change to the marketing authorisation be refused.

What are the consequences of the refusal for patients in clinical trials with Cymbalta/Xeristar?

The companies informed the CHMP that there are currently no ongoing clinical trials with Cymbalta/Xeristar in fibromyalgia patients in Europe.

What is happening for duloxetine used for the treatment of other diseases?

Duloxetine, under the names Ariclaim and Yentreve, is also authorised for use in stress urinary incontinence. There are no consequences on the use of Cymbalta/Xeristar, Ariclaim or Yentreve in their authorised indications, for which the balance of benefits and risks remains unchanged.

http://www.pharmalive.com/News/index.cfm?articleid=579986&categoryid=51#

Coping with Chronic Illness and Disability (Springer, 2007)

Individuals' responses to their chronic illness or disability (CID) vary widely. Some are positive and productive, some negative and self-defeating, and some have elements of both. Coping with Chronic Illness and Disability synthesizes the growing literature on these coping styles and strategies by analyzing how individuals with CID face challenges, find and use their strengths, and alter their environment to fit their life-changing realities.

The book's first section provides readers with the major theories and conceptual perspectives on coping, with special emphasis on social aspects and models of coping with different types of CID. In Part Two, an array of specific medical conditions is covered. Each chapter supplies a clinical description, current empirical findings on coping, effective medical, physical, and psychological interventions, employment issues, and social concerns. This book includes:

• Up-to-date information on coping with high-profile conditions, such as cancer, heart disease, diabetes, arthritis, spinal cord injuries, and traumatic brain injury
• In-depth coverage of HIV/AIDS, chronic pain, and severe mental illness
• Coverage of therapeutic modalities adopted for treatment of people with CID
• Review of the current state of coping theory and research
• Appendix of instruments frequently used in assessment of coping

The editors' skillful balance between theoretical and practical material will help rehabilitation specialists (particularly psychologists, counselors, social workers, and health-care providers) develop new insights into promoting successful coping, and discern new means of changing its less effective forms. Students in the helping professions, as well as individuals experiencing CID, may also find this multifaceted book useful for understanding some of the psychosocial dynamics of living with CID.

http://www.springer.com/psychology/stress+&+coping/book/978-0-387-48668-0

Hospitals Seeing Decline in Paying Patients - NYTimes.com

In another sign of the economy's toll on the nation's health care system, some hospitals say they are seeing fewer paying patients — even as greater numbers of people are showing up at emergency rooms unable to pay their bills.

While the full effects of the downturn are likely to become more evident in coming months as more people lose their jobs and their insurance coverage, some hospitals say they are already experiencing a fall-off in patient admissions.

Some patients with insurance seem to be deferring treatments like knee replacements, hernia repairs and weight-loss surgeries — the kind of procedures that are among the most lucrative to hospitals. Just as consumers are hesitant to make any sort of big financial decision right now, some patients may feel too financially insecure to take time off work or spend what could be thousands of dollars in out-of-pocket expenses for elective treatments.

The possibility of putting off an expensive surgery or other major procedure has now become a frequent topic of conversation with patients, said Dr. Ted Epperly, a family practice doctor in Boise, Idaho, who also serves as president of the American Academy of Family Physicians. For some patients, he said, it is a matter of choosing between such fundamental needs as food and gas and their medical care. "They wait," he said. The loss of money-making procedures comes at a difficult time for hospitals because these treatments tend to subsidize the charity care and unpaid medical bills that are increasing as a result of the slow economy.

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http://www.nytimes.com/2008/11/07/business/07hospital.html?_r=1&partner=rssuserland&emc=rss&oref=slogin

Research into medicinal marijuana grows up - Slate Magazine

This summer, British and Italian researchers found that in a laboratory plate, molecules in marijuana can slay the superbug methicillin-resistant staphylococcus aureus, which recently infected seven babies and four employees in a Yonkers, N.Y., maternity ward, heightening fears of outbreaks in schools and locker rooms, as well as in its more familiar breeding grounds, hospitals and nursing homes. In theory, compounds derived from the cannabis plant could someday serve in topical creams for patients with MRSA or other antibiotic-resistant infections.

This isn't the first time marijuana has tantalized the world as a possible wonder drug. In recent years, compounds in cannabis or related molecules have been shown to slow the growth of lung tumors in mice, decrease hardening of the arteries in rats, and boost the egg-binding capability of tobacco smokers' sperm. Research on the receptors that THC and other cannabis compounds attach to—and the nitty-gritty mechanisms by which they exert their effects—has been booming. So has work on native molecules, called endocannabinoids, that bind to the same sites. These molecular interactions affect a wide range of functions, from appetite to inflammation to the perception of pain.

The onslaught of basic science has helped to separate cannabis from an association with hippies and recreational pot smokers. It has also spurred hopes that these molecules (or similar ones) might prove therapeutic for traumatic brain injury, inflammatory bowel disease, allergic contact dermatitis, atherosclerosis, osteoporosis, and Alzheimer's disease, among others. For all the razzle-dazzle, though, potential treatments frequently seem stuck in perpetual adolescence. Research on traumatic brain injury seemed promising but got mixed results in human clinical trials, while most of the others simply haven't gotten very far in the experimental process.

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http://www.slate.com/id/2203922/?from=rss

Hurry Down Sunshine by Michael Greenberg - Biography - Random House

excerpt

Sally emerges from her room in a thin hospital gown, snap buttons, no laces or ties. She suddenly looks ageless. The only other time I've seen her in a hospital was the night she was born. By that point in our marriage her mother and I were like two people drinking alone in a bar. Not hostile, just miles apart. Yet when Sally appeared, a huge optimism came over us, a physical optimism, primitive and momentarily blind. She was her own truth, complete to herself, so beautifully formed that the jaded maternity nurses marveled at what perfection had just slid into the world. Though she has never set foot in a psychiatric hospital, there is the tacit sense from Sally that she is understood here, she is where she belongs. She acts as if a great burden has been lifted from her. At the same time she is more elevated than ever: feral, glitter-eyed. In 1855 a friend of Robert Schumann observed him at the piano in an asylum near Bonn: "like a machine whose springs are broken, but which still tries to work, jerking convulsively." Sally appears to be heading toward this maimed point of perpetual motion. Her sole concern is to get her pen back, which has been confiscated with most of her other belongings–belt, matches, shoelaces, keys, anything with glass, and her comb with half its teeth snapped off by her potent hair. She initiates an agitated negotiation with the nurses, which immediately threatens to boil over into a serious scene. The nurses confer like referees after a disputed call. Then they grant her a felt-tip marker and march her back to her room.

http://www.randomhouse.com/catalog/display.pperl?isbn=9781590511916&view=excerpt

Family Health with Beatrice Politi - videos on Global News (Canada)

http://www.globaltv.com/globaltv/ontario/story.html?id=762729

Number of kids on medication jumps alarmingly - Most of the illnesses related to obesity - USAToday

The number of children who take medication for chronic diseases has jumped dramatically, another troubling sign that many of the youngest Americans are struggling with obesity, doctors say.

The number of children who take pills for type 2 diabetes — the kind that's closely linked to obesity — more than doubled from 2002 to 2005, to a rate of six out of 10,000 children. That suggests that at least 23,000 privately insured children in the USA are now taking diabetes medications, according to authors of the new study in today's Pediatrics.

Doctors also saw big increases in prescriptions for high cholesterol, asthma and attention deficit and hyperactivity. There was smaller growth for drugs for depression and high blood pressure.

"We've got a lot of sick children," says author Emily Cox, senior director of research with Express Scripts, which administers drug benefit programs for private insurance plans. "What we've been seeing in adults, we're also now seeing in kids."

Type 2 diabetes was once known as adult-onset. But Cox says her records show kids as young as 5 being treated with prescription diabetes drugs.

Cox based her study on prescription records of nearly 4 million children a year, ages 5 to 19, covered by Express Scripts. She says her findings may not apply to the 40% of children who are uninsured or covered by government health plans.

Unless these children make major changes — such as eating healthier and exercising more — they could be facing a lifetime of illness, Cox says.

"These are not antibiotics that they take for seven to 10 days," Cox says. "These are drugs that many are taking for the rest of their lives."

Cox couldn't explain one surprising finding: Most of the increase in drugs for diabetes, attention deficit/hyperactivity and depression was seen in girls. The gender gap was most striking in diabetes: While the number of boys taking medication grew by 39%, the number of girls using them climbed by 147%, Cox found.

http://www.usatoday.com/printedition/news/20081103/1a_bottomstrip03_dom.art.htm

Excess Weight Seems to Boost Breast Cancer Risk - US News and World Report

Obesity can wreck a person's health for many reasons. But for women, too much weight tacks on an additional danger: Studies have linked obesity and breast cancer in a variety of ways.

Doctors aren't sure why this link exists and are trying to figure out what ties weight gain to breast cancer. But they are more and more convinced the link is there, and they are urging women to watch their weight and increase their exercise to help stave off what is the most common cancer among females, nonmelanoma skin cancer aside.

"There are a lot of factors we need to figure out," said Dr. Jennifer A. Ligibel, of the Dana-Farber Cancer Institute in Boston. "There are a lot of things we don't know."

An estimated 182,500 women in the United States will be found to have invasive breast cancer in 2008, according to the American Cancer Society, and about 40,480 women will die from the disease this year. Currently, there are about 2.5 million breast cancer survivors in the United States.

Studies have found that, in general, obesity is linked to cancer. The higher a person's body-mass index (BMI, a ratio of weight to height), the more likely she or he will develop cancer, according to recent research by scientists at the University of Manchester in England. Other studies have found similar links to increased body fat.

Still other studies have found that women with breast cancer are more likely to live shorter lives and suffer a recurrence of their cancer if they are overweight.

For example, in a recent study conducted at the University of Texas M.D. Anderson Cancer Center in Houston, more than two-thirds of women with stage III locally advanced breast cancer were either overweight or obese. The study also found that a greater proportion of obese patients were likely to be diagnosed with a rare and more deadly form of breast cancer, known as inflammatory breast cancer.

Scientists vary in their opinions on why this link exists, and what it means.

Some believe that obesity may make tumors harder to detect, so a woman's breast cancer will be further developed before it is discovered.

"It could be because there's more breast tissue, a lump would be less evident," Ligibel said.

Researchers also believe that the systemic effects of obesity might do something to spur cancer on. For example, obesity or overweight can lead to fluctuations in hormone levels in the body.

"When women are heavier, their estrogen levels are higher," Ligibel said. "That could be a pathway through which weight affects breast cancer. Other studies have shown that when insulin levels are high, there's more chance a cancer will come back."

More ...

http://health.usnews.com/articles/health/healthday/2008/11/02/excess-weight-seems-to-boost-breast-cancer-risk_print.htm

Why the rich and powerful might get substandard medical care. - Slate Magazine

Not long after Sen. Edward M. Kennedy was diagnosed with brain cancer this summer, he summoned his very own group of national cancer experts, a "tumor board," to discuss his case and recommend treatment. The New York Times called his health care "extraordinary" for several reasons: Tumor boards are usually convened by doctors for complicated cases, not by patients, and rarely is it possible to summon "more than a dozen experts," as Kennedy did, on short notice. While it may not be surprising that someone with fame, stature, or wealth would receive more attention when ill, it seems unfair that he should get better medical care than the rest of us.

Actually, he doesn't. Although the senator has unlimited access to expert doctors, he suffers from a different disease that rarely afflicts soccer moms but can be even deadlier than cancer: very important person syndrome. VIP syndrome strikes when doctors and nurses treat VIP patients differently—and, in the end, the medical care is worse, not better. Because VIPs are special, doctors and nurses deviate from usual protocols. As a result, the patient receives something other than the standard of care.

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http://www.slate.com/id/2203331/pagenum/all/#p2

Doctor and Patient - Medical Student Burnout and the Challenge to Patient Care - NYTimes.com

Not too long ago, I read a paper titled "Burnout and Suicidal Ideation Among U.S. Medical Students" in The Annals of Internal Medicine. It brought back a flood of memories.

Medical school was not easy for me. I knew that I wanted to become a doctor to help people, but I had given little thought to the process. I was poorly prepared for many things: the pressure to excel in ways that seemed so far from caring for people; rapidly mounting debts I signed off on every semester; a roller coaster existence from chronic lack of sleep; hazing from the more experienced students and residents; and the realities of patient suffering despite my best efforts.

Even surgical residency, despite the relentlessly long hours, seemed so much closer to what I wanted to do.

Some of my professors tried to "humanize" the process. They invited us to dinner in their homes, supported our extracurricular efforts to set up health screening clinics in low-income neighborhoods, and tried to make our basic science courses more relevant to working with patients. But sitting where I am now, as someone who teaches medical students and who loves helping others as a doctor, I can understand the challenge they faced. Given the fire hose of information medical students must learn in just four years, how does one ever gently take a sip?

Despite my teachers' efforts, I was about as miserable in medical school as I had ever been. I felt alone. Neither I nor my classmates could admit to failure, and the last thing I wanted to do was to let anyone but my closest friends know just how unhappy I was. Success in medical school was the first step to a future of helping others, and I was not about to jeopardize that.

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http://www.nytimes.com/2008/10/31/health/chen10-30.html?em=&pagewanted=print

The Safety Gap - Can the F.D.A. Ever Hope to Police Chinese Meds? - NYTimes.com

In the belly of an industrial district south of Lyon, France, just past a sulfurous oil refinery and a synthetic vanilla plant, sits a run-down, eight-story factory that makes aspirin, the first pharmaceutical blockbuster. The Lyon factory is the last of its kind. No other major facility in Europe or the United States makes generic aspirin anymore. The market has been taken over by low-cost Chinese producers. Even Bayer, the German company that created aspirin in the 1890s and has fought for more than a century to distinguish its product as the most trustworthy one, now has backup supplies from China.

The Lyon plant is owned by a French chemical giant named Rhodia that has been making aspirin since 1908 and still accounts for more than 25 percent of the world's aspirin market. But now a century after its entry into the business, the company intends to quit making aspirin altogether. The plant was last renovated in 1992, and it would need an upgrade to continue operating, an investment the company can no longer justify in what has become a cutthroat business. In fact, Rhodia is closing another factory about 40 miles to the south. This one makes the painkiller acetaminophen, which is found in Tylenol. It, too, is the last such facility in Western Europe.

In some ways, this is a nonevent. European factories close; Chinese ones open. Consumers like their commodities cheap, in the case of aspirin as with everything else. China now produces about two-thirds of all aspirin and is poised to become the world's sole global supplier in the not-too-distant future. But are the Chinese factories safe? Who knows? The U.S. Food and Drug Administration, the European Medicines Agency and other competent government regulators rarely, if ever, inspect them. (By contrast, Rhodia's plant was last inspected by the F.D.A. in July and is routinely inspected by one country or another.) Companies that import Chinese pharmaceutical ingredients, including aspirin, are required to test the supplies before using them, and some send private inspectors to China to ensure that suppliers use adequate controls. No pharmaceutical maker wants its name to become synonymous with disaster, and the vast majority of drugs that are consumed in the United States are safe. But some industry executives told me that price sensitivity in the generics industry makes it more difficult to fully vet their low-cost suppliers.

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http://www.nytimes.com/2008/11/02/magazine/02fda-t.html?ref=magazine&pagewanted=print

Podcast: WNYC - The Leonard Lopate Show: Drugs and Deals: Lobbyists in Healthcare

The healthcare industry spent more than $189 million on lobbying the
federal government in 2007, up more than 32% from the year before.
Over the past decade pharmaceutical interests alone have spent more
than $1 billion on federal lobbying. We take a look at the sway
healthcare lobbyist have over Congressional legislation, and what
that might mean for the proposals of both Obama and McCain. Chris
Frates is Lobbying Reporter for Politico; Bill Buzenberg is Executive
Director of the Center for Public Integrity.

http://www.wnyc.org/shows/lopate/episodes/2008/10/29/segments/113888

Los Angeles Times: A guide for Americans seeking affordable medical treatment abroad

When Andy Dijak injured his right knee playing tennis, he wasn't surprised that he needed surgery. "It swelled up like a balloon," said the 50-year-old West Lake resident.  The real shocker was the price tag: $12,000 to $15,000 to repair tattered cartilage. Dijak, a creative director for an entertainment company, has no health insurance, so he started shopping for a deal. 

He found it in the northern Mexico city of Monterrey at Christus Muguerza High Specialty Hospital, owned by Dallas-based Christus Health. Here, the staff treated him more like a big shot than a bargain hunter. An English-speaking employee picked him up at the airport. Dijak recuperated in a private hospital room with a flat-screen television and a view of the peaks of the Sierra Madre. His surgeon recorded the operation on video and gave Dijak a DVD copy for his peace of mind. Total cost, including airfare: $4,500.

"I got better care there than I would have in the United States, unless I were a billionaire," he said.

Americans have long been willing to leave the country for bargain face-lifts and cut-rate dentistry. But now the availability of top-notch medical services at low cost is enticing a growing number of U.S. patients to developing nations for more sophisticated procedures. Most, like Dijak, are obtaining elective surgeries for ailments that aren't life-threatening. Increasingly, they are seeking treatment for more serious conditions, including heart maladies and cancer.

Last year, 750,000 Americans traveled abroad for care, according to estimates by the Deloitte Center for Health Solutions, a Washington-based research center that's part of the consulting firm Deloitte & Touche. Other analysts say the numbers are lower. But hardly anyone disputes that medical care, once a highly local business, is going global like never before. By 2010, Deloitte projects, 6 million consumers a year will venture outside the United States for medical treatment.

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http://www.latimes.com/business/la-fi-cover2-2008nov02,0,4808395,print.story