Moving the Goal Posts to Catch the Ball and Other Hazards of A Chronic Fatigue Syndrome Treatment Trial

When it comes to offering patients high-quality care for a poorly understood disease, solid, well-funded research, medical education, and respect go a long way. In a masterful report today in STAT, Julie Rehmeyer sets the record straight on chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME). She specifically covers the many pitfalls in the landmark UK PACE trial. Rehmeyer is far from the only critic of this research.

The trial serves as a model for how not to conduct a clinical trial and criticism of it has been abundant, as Rehmeyer explains. Worse still, its conclusions that exercise and cognitive behavior therapy are effective have underpinned clinical practice guidelines around the world. That’s a bad thing because the conduct of the trial was questionable, making its recommendations moot and harmful to patients. Read her story. It’s a longread, but well worth the effort.

But I’d like you to take away from this post key problems with the PACE trial. People with ME and their caregivers need all the help and understanding that they can get. Also, many people won’t read Rehmeyer’s piece. Therefore, the more outlets that understand the neglect and misunderstanding about it, the better. Also, this blog is quite interested in the patient point of view on how to be cared for, a topic that remains undercovered and unappreciated. Note well: Rehmeyer and other ME patients add a lot to the discussion and many research scientists agree with her concerns.

 Patient Experience Departs from the Trial

Julie Portrait

As Rehmeyer explains, when she first got wind of the trial, its sheer breadth made it seem potentially valuable. “It seemed like a great study – big controlled, peer-reviewed…,” she wrote. But she delved deeper because the findings did not jibe with her experience and others living with CFS/ME.  She continues: “The hallmark of ME/CFS is that even mild exertion can increase all the other symptoms of the disease, including not just profound fatigue, but also cognitive deficits, difficulties with blood pressure regulation, unrestorative sleep, and neurological and immune dysfunction, among others.”

The trial concluded that graded exercise works – the exact opposite of how patients with CFS/ME describe their endurance. “Staying within my ever changing limits” seemed the safest course for Rehmeyer and others to stop them from spinning down into phenomenal debilitating illness.

The other cornerstone conclusion,  that cognitive behavioral therapy, or training oneself to think positive, become more active, and ignore their symptoms, felt enormously insulting to Rehmeyer and other patients, especially when other science pointed to other clues to what underpins the disease.

What’s become abundantly clear is that besides patients like Rehmeyer, immunologists have identified important patterns in the immune system and physiologists have found “highly unusual physiological changes in ME/CFS patients after exercise,” Rehmeyer points out.

There’s certainly been a long history in medicine of viewing some patients as malingerers, i.e. that they don’t want to get well. Although I haven’t seen Rehmeyer and others discuss this quite this way, I wonder whether the investigators were predisposed to viewing the patients as malingerers. I’ll be honest: I am all for making the best of a situation and trying to look on the bright side, but I am closer to Barbara Ehrenreich here, who wrote the recent book Brightsided: How Positive Thinking is Undermining America. I’ll leave it to others to explore whether the PACE investigators were unfairly biased from the get-go to think cognitive behavioral therapy must work. I am sure that many similar and some different incentives motivate health researchers pinning their hopes on it, but that’s just a hunch.

But when trials like PACE become the quintessential trial for teaching clinical practice guidelines, explanations grounded in science are tossed to the wind or not pursued.

Wouldn’t it be wonderful if research funds were allocated into the pathophysiology of ME/CFS and effective treatments were developed? Slowly, this is starting, and with more attention to the disease, more is bound to come.

PACE Hazards

What’s worse is the highly unorthodox way the trial was conducted. Above, I mentioned moving the goal posts to catch the ball. In midstream, investigators lowered the bar for self-reported recovery. Rehmeyer writes:

“Their revised definition of “recovery” was so loose that patients could get worse over the course of the trial on both fatigue and physical function and still be considered “recovered.” The threshold for physical function was so low that an average 80-year-old would exceed it.”

Rehmeyer also raises questions about the interaction between the researchers and the patients. Specifically, the way patients were asked about their self-reported symptoms also seemed questionable in leading to unfounded conclusions of marked improvement.

It Takes A Movement

To bring you up to date, PACE has been a moving target. Since the trial findings were published in 2011,  patients, scientists, and critics have fought over the merits of the trial in newspapers, peer-reviewed journals, and blogs. The times they are a changing, albeit slowly.

A Freedom of Information Request for the trial investigators to release all the data to patients succeeded in the UK. Alem Matthees, a patient from Perth, Australia, who obtained the data and led the analysis, said that the differences between groups were within the range of chance variation, and indicated no benefit of the therapies.

Together with patients, statistics professors Bruce Levin of Columbia University and Philip Stark of the University of California Berkeley have recalculated “recovery” statistics. In contrast to the study authors’ claims of recovery rates of 22%,

 the new analyses found that only 4% of patients who received exercise therapy, and 7% who received cognitive behavioral therapy (CBT) recovered, while 3% of a no-therapy comparison group did so.

An evidence review sponsored by the US Agency for Healthcare Research and Quality and finished this year, also reveals that PACE and other research into ME is wanting.  “More definitive studies are needed to fill the many research gaps in diagnosing and treating ME/CFS,” write the authors of the systematic review. On key criteria, the evidence to back widespread adoption of recommendations from previous research remains weak.

ME/CFS  is just the kind of topic that the US Patient Centered Outcomes Research Institute (PCORI)might support, if patients mounted a successful campaign for it as a priority topic.

A movement has grown and patients have every right to be indignant. All along the way, proponents of the trial have raised questions about tactics and anger coming from irate patients. But patients have been largely helpless and disrespected until now, and quibbling about their tactics sounds like a side show.

On September 27, rallies are being organized in 25 cities around the world to press for research funding for ME/CFS. The battle to garner attention to this poorly understood illness is moving forward.





Appendicitis in America: Time for Practice Change?

Chances are good that most readers have had personal experience with appendicitis. Appendectomy is the top inpatient surgery for kids and it far outpaces all other pediatric surgeries. Also, appendicitis is the most frequent reason adults make it to the emergency room. When people worry about their healthcare, appendicitis may seem like small change, mundane compared to big worries like chronic or debilitating conditions, and easily fixable by having your appendix surgically removed. Then it’s over.

However, the sheer volume of the surgery, done routinely and automatically in most of America, against new data that point to equivalent efficacy and a lower complication rate with antibiotic medical management for uncomplicated appendicitis make it an interesting case study of how medical paradigms change.

The tide has shifted in Europe towards using antibiotics as first-line, but probably because national health insurance programs use science much more to guide matters of the public health. In the United States, paradigm shifts towards less use of surgery come slowly and with a great deal of resistance from those threatened by the shift.

An Emblematic Case in Point

I became keenly aware of how uninformed most patients are when a friend over 70 years-old called me from the emergency room on a spring Saturday afternoon, telling me a surgeon wanted to operate on him in an hour for uncomplicated appendicitis. My initial reaction was to tell him to wait a minute because I remembered recent journal articles, notably a Finnish randomized trial suggesting antibiotic therapy had a good shot of curing the appendicitis, without the risks of surgery and an extended recovery. Appendicitis can recur in a minority of patients after antibiotic therapy, but carefully managed, one year out, there is usually no recurrence.

My friend, a skeptical medical writer to boot, had indicated that he wanted more information before he was shooed into surgery. I will say nothing more about his story because he has promised a blog post and will let him tell his story. Suffice it to say that he went the antibiotic therapy route and I am pretty darn sure that it would not have entered the picture if we hadn’t suggested it.

Decision Aid Research: Enter PCORI

This week, I received an announcement from the Patient Centered Outcomes Research Institute that they were funding research into testing a decision aid to help parents figure out what to do when their child has appendicitis. It’s a step in the right direction, but its ultimate value will depend on how widely it is used in the real world.

Decision aids purport to present the options to patients and/or caregivers so that patients can make the decisions that best suit them, based on their personal preferences, the science, and the uncertainties. In the past, they have been introduced when procedures are widely used, costly, when a paradigm shift in medicine is emerging, and when the best strategy seems debatable. Decision aids have been used for things like deciding what to do in the face of a diagnosis of prostate or breast cancer or whether or not to have joint (hip or knee) replacement.

Decision aids have been linked to more satisfactory outcomes, but I hardly think that they will provide the nexus of change in appendix care. I have seen no evidence that they are even used in the institutions that develop them. Nonetheless, they are a start.

A hellufa lot more public education will likely be needed to shift medical practice. I am sure that Rose Kushner and the women’s movement had more impact on reducing unnecessary total mastectomies than decision aids would have, but all is valuable.

The Decline of Surgery: A Moving Target

Robert Colgrove, MD, Division of Infectious Diseases, Mount Auburn Hospital, and Assistant Professor of Medicine, Harvard Medical school, captured the full measure of the shift towards treating appendicitis with antibiotics, rather than surgery.

“Having most of these managed medically means hundreds of thousands of operations averted in the US alone,” he said. “Along with the demise of routine tonsillectomy, it represents a huge reduction in the fraction of otherwise well children who get an operation.”

It’s not just appendectomies that are likely to decline going forward, but other surgeries are also declining as we move ahead, because medical management is showing advantages in lower complication rates, shorter recovery time, and cost.

But change will be resisted. Take gall bladders. “The most definitive way to manage cholecystitis (an inflamed gall bladder) is with cholecystectomy (removal of the gall bladder), a well validated procedure with over a century of experience to back it up,” Colgrove told me. “The best way to manage it now is very much an open question and a moving target. Classically, most people with acute cholecystitis would go on  to have recurrent and/or chronic cholecystitis, so the argument has been that you might as well just go ahead and take it out.”

Colgrove begs to differ. “As medical management improves, though, it is not at all clear that that is true any longer. Current data suggest that most people with uncomplicated cholecystitis do well with non-surgical management, but it will take a few more years before we really know the long-term implications. This is a big deal, representing a huge change in the management of one of the most common surgical procedures, so it is natural that the medical culture is taking some time to absorb it.”

From my vantage point as a public observer, it bothers me that my friend in the emergency room was set to be routed directly to surgery. When will patient safety people be available to consult with patients, some of whom might have fewer risks with an antibiotic course of action?

There are numerous other issues worthy of public discussion tied to appendicitis in kids and adults, too large for a blog post here.

My computer went belly-up this morning and I wanted this out before my short vacation. I regret the lack of links on this post, more comprehensive attention to the latest research, and the role of excessive imaging in evaluating appendicitis – topics covered previously here.

Please share your point of view in the comments below. We need a movement to move practice rationally forward.





AARP: Stakeholder for Waste and Moneyed Interests?

AARP, you lost whatever presumed credibility you thought you had with one article in the current issue of your magazine. I am talking about the hard copy of “All the President’s Scans: Our Commander in Chief Regularly Gets An Extensive Physical: Should You?” – part of your Spring 2016 Health Special in AARP: The Magazine, out this weekend. The hard copy is far more slick and glossy than what’s online, replete with pics of the three most recent presidents getting comprehensive physicals for everything under the sun, with smiles on their faces. These were not online. BTW, readers, you can get a copy of it at your local library if you don’t see it at your doctor’s office or are not getting it as an AARP member. Readers note: to get a Medicare Supplement, AARP requires that you join AARP.


Pitching High


Readers over age 50 (AARP’s target audience) might be tempted to look for an executive physical after reading this article. AARP tells you right away where to go for it in the first paragraph: “Cooper Clinic, Cleveland Clinic, UCLA, Duke and many other major hospitals offer them,” the author writes, warning you that “you could pay upward of $2,000 to $3,000 out of pocket for this.”

Like concierge care before this, executive physicals can embellish a doctor’s base considerably and enlarge what people pay for healthcare. First, a sliver of the upper middle class is conned to pay for these tests because, after all, what’s more important than your health? Pretty soon, demand increases broadly and prices go up for all.

As Good as a Cruise

The nuts and bolts of this executive physical are written about like brochures for a cruise. Nothing but upbeat information, you’ll find here. No downsides. It’s clear that AARP will satisfy many of its funders: for example, academic medical centers, providers looking for volume, and purveyors of imaging and screening tests. But those groups have their own stake and it conflicts with that of aging Americans, no matter what their health status.

Here’s the potpourri of tests that AARP claims “could help” you and provide superlative care:

  • Blood pressure readings taken all day long;
  • Blood test and urinalysis;
  • A thorough head-to-toe physical exam instead of the “old-fashioned once-over;”
  • Specialist exams all done in one day;
  • Multi-expert Q&As;
  • Body fat tests;
  • Cancer screenings, including mammography, colon, and PSA – and even a total-body CT scan, with the caveat that “some detractors think that ultra-early detection can lead to unnecessary treatments.”
  • Eye exams, which could lead you to “new medications that may help stop the spread of macular degeneration, one of the leading causes of blindness in older people” and blood vessel changes in the eyes, suggestive of uncontrolled hypertension.
  • Strength and flexibility assessment, which can lead you to physical therapy for pain relief, balance improvement, and strength improvement;
  • A stress test – EKG showing early heart problems;
  • A sit-down to summarize all the above.

Harm and The “Detractors”

The absence of attention to how so many of these tests have been demonstrated to be wasteful and even harmful is concerning.

AARP, you owe it to your readers to not masquerade advertisements as journalism. Aging Americans have shrinking pocketbooks and this “advice” is a disservice to readers. You scoff at the so-called “detractors,” as if they are few when they are many, completely overlooking the body of scientific research, clinical practice guidelines, and state of knowledge about these tests, which many, as opposed to few, question. Major health authorities question many of these tests, discussed a bit in this blog in numerous posts, and many other places. Overuse is concerning, harms are unacceptable.

For policymakers looking for stakeholders to represent aging Americans, please look outside of AARP. It does not represent us. I submit that AARP’s voice is with waste and the moneyed interests in healthcare, the providers, the establishment, and white Americans aspiring to be part of it.



Readers might be interested in more nuanced discussion of these issues, as covered previously in this blog:

Cardiovascular Care and the Bush Effect

MR Imaging, Electronic Test Ordering Creates Waste

Back Pain Trends Worth Reversing

 What’s Next for Prostate Cancer Screening and Treatment?

Caveat Emptor: Testosterone Replacement Therapy Ads Soar


..and many more.


Finally, my shameless self-promotion here, but PLEASE take this seriously.


I need more paid, honest work to do! Please contact me! I am not ready to retire.


Economic Repercussions Prove Powerful in Stopping Hateful Public Health/Quality of Life Laws

It’s hard to keep up with the regressive state laws that threaten the people’s health and quality of life. Women, LGBT individuals, and people of color are popular targets. There may be a silver lining though. Just this morning, the NY Times reported corporate sponsors are thinking twice as groups mobilize to #dumpTrump, demanding that corporations separate themselves from Trump and the Republican National Convention. Coke already shrunk its $  substantially. More sponsors are expected to join in. Kind of makes me hungry for a Coke, all that sugar and all. This is special.

Economic boycotts have also been announced following North Carolina’s passage of the egregious HB2, which eliminates all new LGBT protections.  Although it’s been oversimplified into the “bathroom bill”because it disallows transgender people from entering bathrooms of the gender they identify with,it is more wide-reaching, and also takes away legal protections for LGBT individuals in the state. Last February, Charlotte NC passed a nondiscrimination ordinance. That will be made moot with NC Governor Pat McCrory signing the law.

New York State, Vermont, Washington, the City of Seattle, have announced boycotts against the state, and by the time you read this, we’ll see many more. The City of Atlanta has come out punching, saying the NBA’s All-Star Game should be moved out of Charlotte to Atlanta. Tourism, sports money are at stake.

North Carolina is already facing economic woes as a result of its outrageous positions on abortion rights. The Women’s Right to Know Act, passed in 2011, forced women opting for abortions to listen to a narrated ultrasound within 4 hours of a scheduled abortion. The good news is that the State lost a Federal lawsuit to stop this, and they now must pay out $1 million from savings in an emergency fund for legal fees, according to a News & Observer report.

Economic sanctions are proving  a lever for change, for getting corporations on the side of the people’s health. Interestingly, Atlanta was at risk of losing rights to the upcoming Super Bowl, given fair warning that passage of its regressive anti-LGBT bill would have repercussions. Then, last week, that bill was not signed into law, a victory for the people of Georgia, and LGBT health and safety.

I always think about the people in states proposing regressive legislation. The Moral Monday movement in North Carolina has been out front for quite awhile objecting to these horrendous laws that harm the public’s health. I applaud the movement. Although I wish that there was a better way than boycotts, I have to say I am delighted that people have been organizing successfully, that businesses are taking note, and that we just might stem the tide of the nasty rhetoric and legislation afoot in many parts of this nation.

Do you have thoughts on how we can restore protections now endangered? Please join the discussion below.








Homeless Youth and the Chicago Youth Storage Initiative: This Project Needs Your Support

Sleep Out Chicago, Nov. 20, 2015. Credit: Kat Ferguson.

Sleep Out Chicago, Nov. 20, 2015. Credit: Kat Ferguson.

Homelessness may seem remote to you today as you lounge around a comfortable home celebrating Christmas, with presents and ease. Even if you are not celebrating Christmas, this week and next, many of you are likely to spend time in someone’s home, taking for granted that you have a chance to relax comfortably. But the economy, housing, and jobs have not been kind to many. Today, I ask you to give back to homeless organizations, specifically highlighting the Chicago Youth Storage Initiative, which is raising money so that homeless youth can safely store their belongings in lockers.

Several thousand dollars has been raised for the project, but your donation will help move this program forward.

Your donations accepted thru Dec. 31:  fighting youth homelessness. Pick one of the agencies working on this and donate at link here.

Over the next 18 months, the Youth Storage Initiative is putting 250 lockers into drop-in centers and shelters across Chicago. Each locker will be large enough to hold three suitcases.
  Why the Youth Storage Initiative?

“For young people experiencing homelessness and housing instability, access to safe and secure storage options for personal belongings – such as clothing, school books, keepsakes, and legal documents – is a daily, often hourly, stressor,” says Lara Brooks, Director of the Chicago Youth Storage Initiative. As for the magnitude of the problem, the Chicago Coalition for the Homeless estimated that in the 2014-2015 school year, 13,054 families were homeless, with fewer than 125 families finding permanent affordable housing annually, with about 22,000 homeless students. Imagine where you can keep important documents and valuables, job-interview clothes, or textbooks if you don’t have your own home or safe place to leave them.

 The Youth Storage Initiative grew out of an LGBT Homeless Summit, organized by Windy City Times and its publisher and Executive Editor Tracy Baim. Although LGBT youth have special problems, the Youth Storage Initiative is available to all youth, regardless of gender identity.

Storage Initiative Backers

Fundraising for the project was buoyed by Sleep Out Chicago, held Nov. 20 this year, in Chicago. The program would not be possible without the generous support of Marianne Philbin of the Pierce Family Foundation, Debbie Reznick of the Polk Brothers Foundation, Tracy Baim, Publisher, Windy City Times, Lara Brown, the Chicago Youth Storage Initiative, and a much-needed grassroots campaign in Chicago.

Vaness Davis, Credit: Hal Baim photography.

Vaness Davis, Credit: Hal Baim photography.

Wishing all a happy and healthy 2016 – and a permanent, affordable housing for all in 2016!

Blowing the Whistle on Toxic Toys
& Why I Am Giving Back

Toxic toysPhoto: Toxic toys for sale this holiday season in New York City. Credit: WE ACT for Environmental Justice, New York, NY.

It’s 36 hours before I go to a Christmas dinner, where I plan to bring gifts to two lovely girls. After buying books for the occasion, I had second thoughts, thinking that books might bore them. So I added in an inexpensive, make-your-own jewelry kit and another kit with lots of paint. Then this happened. Those girls will never see those kits because I fear that they are probably toxic. I worry about the people who manufactured them, who will surely have longlasting toxic effects like the “radium girls,” who made radium watches.  The toys look a lot like some of the items pictured above, demonstrated to be loaded with toxic metals, by WE ACT for Environmental Justice, the Center for Environmental Health. The toys are for sale in New York City stores this holiday season and they are toxic. A coalition of these groups, together with parents, and business representatives released their report Dec. 17 on New York City’s City Hall. I applaud them. It’s likely toxic toys are for sale in your community too.

I am making a tax-deductible charitable donation to WE ACT for Environmental Justice. You can donate here.

Readers, this post is not something that I planned with them at all, but stems from considering forward-thinking groups that engage the public and communities around important issues in the public’s health. You’ll be hearing about other groups from me here until the end of the year. I suggest that you poke around WE ACT’s website to see what valuable work that they do. You can read about their theory of change here. WE ACT is far from a single issue group. Its work encompasses environmental justice in the broadest sense: clean air, indoor exposures, reducing waste, pests, and pesticides, affordable, equitable transit, good food in schools, open and green space, as well as stopping toxic products from going to our communities. WE ACT’s work extends to Washington DC, where they are making a dent on the national dialogue on the public’s health.

It’s time we gave back to the groups that have been organizing for the public’s health and protecting the public’s health. If we don’t join forces for change, we are going to be living with more toxicity than we can stand. The Flint Michigan water supply never should have poisoned kids with lead. Donating is love, I read somewhere this week.

Enjoy the holidays! Make your tax-deductible donation to WE ACT here.

DCIS: Overdiagnosis for Some,
But Breast Cancer Death Rates in Young and Black Women Troubling

Ductal carcinoma in situ – known more by its abbreviation DCIS – has been a term mired in controversy for decades. Over the years, it’s been termed “stage 0” breast cancer, “precancer”, and skeptics have gone so far as to say it is perhaps not much of anything. Before the advent of mammography, the proportion of women with DCIS was as low as 3%, but now 20% of women diagnosed with breast cancer have DCIS. That’s why this morning’s news, about the evolution of DCIS, should give women and their doctors pause about how they have approached a DCIS diagnosis.

In short, Steven A. Narod, MD, and colleagues, analyzing retrospective data on nearly 109,000 women from the Surveillance, Epidemiology and End Results (SEER) database, found the following after a diagnosis of DCIS:

  • Overall, 20 years later, the breast cancer mortality rate was 3%, whereas, ten years after, it was 1.1%;
  • Black women were an exception, with a 7% mortality rate;
  • Women diagnosed before age 35 also had a higher rate of 7.8%;
  • Using radiation or mastectomy did not prevent deaths;
  • Preventing an invasive cancer on the same breast as the DCIS did not prevent death from cancer

The researchers analyzed data from a large database of women diagnosed with DCIS between 1988 and 2011 using data from cancer registries across the United States, The paper is published online today in the peer-reviewed JAMA Oncology.

Addressing the big picture, Dr. Susan Love, Dr. Susan Love Research Foundation, told PatientPOV: “This is yet another argument that we shouldn’t be overtreating. this is more support for doing less.” However, she added: This clearly does not apply to every woman. This is just an observational study, not a randomized study. You also have to study what accounts for the higher death rates in young and black women. Further research should explore what accounts for this difference, including looks at the anatomy, biology, and screening practices.”

An inadvertent casualty of the fight against overdiagnosis is that patients who do not fit that profile are overlooked. Just as overdiagnosis can spell waste and harm, the health care community must no longer sweep under the rug bad health outcomes for subgroups. It’s not just a footnote. Failure to delve deeper inadvertently fosters continuing health disparities and inequality.

From Bleak House to My House: A Second Look at Vitamin D

This morning, I noticed that UK news was alight with stories about how the UK National Health Service and NICE are recommending daily vitamin D. In the UK, they are giving out low-dose vitamin D like chocolate at drugstores, groceries, and at your PCP. So it gave me pause after my last post.

First, I wondered: is it really that much more bleak in the UK that the evidence-based authorities are pushing vitamin D so aggressively with certain high-risk groups? Then I thought: did the University of Wisconsin study on postmenopausal women that I wrote about really pan vitamin D supplements? Could the researchers have done better in informing the public. I doubt the public got the story clearly.

I reached Deborah Grady, MD,Professor and Associate Dean of Clinical and Translational Research, at University of California San Francisco,  today, who wrote a companion short commentary in JAMA Internal Medicine on the University of Wisconsin study. I asked her for clarification on the UK/US points of view. She responded: “I don’t think that there is much argument about low-dose vitamin D. [400 IUs per day] of vitamin D is safe, pretty cheap, and might be helpful. The argument is really around much higher doses.”

Meanwhile, today’s US papers were less favorable on vitamin D, referencing  the JAMA Internal Medicine paper.. I asked BMJ’s Richard Lehman for his take on this. He responded: “I have some vitamin D on my desk and I take it occasionally. That’s what they call a British compromise.” That’s an unfamiliar term for me, but a UK-trained doc explained it to me this way: “it’s a political compromise that gives everyone a little bit of what they want and holds the peace for a very long time, but offers no real solution.”

I have spent most of today diving through arcane medical stories that probably could have been more useful for readers.  Perhaps it is unrealistic to hope that vitamin D advice could be as clearcut as the bulleted list from NICE below.

According to NICE (National Institute for Health and Care Excellence), the listed groups below are high-risk groups for vitamin D deficiency and it is these groups that UK public health authorities are reaching out to with enhanced vitamin D access:

  • All pregnant and breastfeeding women, particularly teenagers and young women
  • Infants and children under 5 years
  • People over 65
  • People who have low or no exposure to the sun. For example, those who cover their skin for cultural reasons, who are housebound or confined indoors for long periods
  • People who have darker skin, for example, people of African, African–Caribbean and South Asian origin.

All this input and I haven’t been away from my desk all day. I mean zero time outside, in the sun. It’s just about sundown. Perhaps it’s tantamount to living in the UK. I suppose I should try to change that – although I am not sure how.


Vitamin D and Postmenopausal Women:
Another Case of Overuse?

If you talk to postmenopausal women, you learn that a large proportion of women are told to take vitamin D to bolster bone health, prevent osteoporosis, and fractures. This was used so widely in New York City that a doctor said to me two years ago with a straight face: “There’s something about postmenopausal women in Manhattan that the vast majority of women have low vitamin D.”

In today’s JAMA Internal Medicine,  University of Wisconsin researchers report results from a randomized, double-blind, placebo-controlled trial, refuting the target of 30 ng/mL and questioning the benefit of both low-dose and  high-dose vitamin D therapy on enhancing bone mineral density, muscle function, muscle mass, and falls – finding that it was no better than placebo. The study tested outcomes at one year with high-dose, low-dose, and placebo.

Adequate vitamin D levels are controversial, but this study rejected a target of 30 ng/mL.

It may be a hard pill to swallow for women, who have long feared potentially disabling hip fractures. Many think with aging, more medications are needed.  I spoke with a few friends diagnosed with low vitamin D about the research. They told me that they would rather be safe than sorry and would consult with their doctors.

Documenting no added benefit to a widely used drug is an important first step in changing practice. However, I wonder if more research needs to be conducted on patient perceptions of aging, hazards on the horizon, and imperatives for prevention. Simply documenting inappropriate use or overuse without attention to widely held beliefs may not be sufficient to guide change.

On the Skyrocketing Costs
Of MS Drugs: A Patient Point of View

Last week, Daniel M. Hartung, PharmD, MPH, and coauthors, published an open-access article in Neurology on astronomical increases in disease-modifying drugs for multiple sclerosis (MS) –many developed decades ago. Notably, they report that first-generation drugs — now cost about $60,000 per year, when they originally cost about $8,000 to $11,000. Copaxone is an injection-based therapy. The original Copaxone came out in the 1990s and was part of the first-generation of disease-modifying therapies for MS. It required daily injections. Within the past few months, Teva-Sandoz introduced a new longer-acting brand formulation. The new version is injected three times per week and the company hopes to switch all on the older brand to the new short-acting brand. In fact, an ad on the Copaxone home page makes a compelling argument for the new brand: “With the 3-times-a-week dose, experience 208 fewer injections per year than with daily COPAXONE® 20 mg.” Yet just as this was going on, Teva-Sandoz got FDA approval for a generic version of Copaxone. Yet, Teva had long been adamantly opposed to a generic. What will happen to the pricing and affordability of MS drugs like Copaxone? When will the generic become available?

Patient POV asked a person with MS since the 1990s what he thought of these issues. David asked that his last name not be used. He tried one of the interferons for his MS shortly after he was diagnosed.He has been on Copaxone since 1999 and his MS has been stable. He told Patient POV: “The interferon didn’t help at all. I had side effect and flares with some disease progression.”

Learning that the first-generation MS drug prices are escalating far greater than inflation, what are your thoughts?

These are first-generation drugs that were developed a very long time ago. I don’t think the price hikes are defensible. The research and development costs are long since recovered. The manufacturing costs are not that high. The price in Europe might be a better reflection of the ‘real’ costs of the drug with a reasonable profit. David worries about people without insurance who don’t get the benefit of any reduced price an insurer negotiates. (David knows that his insurer and PBM negotiate the best rates and then establish a copay accordingly.)

David raises another reason why he thinks the price hikes are excessive. It’s not as if these drugs are orphan drugs where the market is so small. There is a significant worldwide patient population.

What do you think about negotiating prices for drugs?

 I know that when the Accountable Care Act was being considered, this came up frequently, but obviously the government has shied away from negotiating best prices, except for state Medicaid. It seems like prices go up as the market can bear and it is very hard to rein in pharma. It’s certainly a deal breaker for the new hepatitis C drugs. I wish that Medicare D would allow negotiation for better prices.

What disease-modifying drug are you on? How long have you been taking them and how interchangeable do you think these medications are?

 I have been on Copaxone since 1999. For two years before that, I tried another drug. Not only did I have terrible side effects, but I continued to have relapses with that drug. I think that patients react differently and should get the drug that gives them the best outcomes and quality of life. It can be hit-or-miss for a person with MS to find the best disease-modifying drug.

A few months ago Teva introduced its three times per week, long-acting Copaxone. Teva hopes to move all Copaxone users to this formulation. Is this something desirable?

Yes. I went on it a few months ago. It helps to not have to inject myself so frequently. I have scar tissue in areas where I have injected frequently. Another advantage of the three-times-weekly dosage is that the shots are less intrusive when I travel. But 99% is getting away from the daily shots that can be uncomfortable.

Teva/Sandoz has not said when it will release generic Copaxone. In fact, there have been numerous attempts to block its introduction. Do you think that generic Copaxone will get much market share?

Teva might have staked out its claim to market share by introducing a new dosage for Copaxone [its brand].  Sandoz has yet to establish a retail price for the generic version.  Also, if PBMs can get better pricing on the generic then there might be pressure to switch.

Have you had to go through any hoops with your insurer to get your Copaxone over the years?

Until quite recently, I needed to get prior approval for Copaxone every year for 15 years. I don’t know what my insurer was thinking. This was very taxing. It took my doctor multiple attempts to get prior approval, sometimes hours on the phone, with faxing, and misplaced papers. There were a couple of years where I was running close to running out of my medicine, which was an additional stressor. Finally, I am at the point with my insurer where the Copaxone goes through year after year without these issues.

That sounds incredibly taxing.

Yes, and if you add to this that many people with MS have secondary conditions and must take additional medications, the red tape to get your needed meds can be endless. Obviously, this can trigger MS symptoms and wipe you out.