Category Archives: General Health

Upside Down Incentives in Pharmaceutical Development –Profit over Patients

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A good read on why cheap effective drugs may not be coming to the market in the U.S. –as well as solutions. (Full text: AR Kellermann, NR Desai. JAMA. Published online August 17, 2015. doi:10.1001/jama.2015.10114)

Here’s an excerpt:

In 2003, Wald and Law proposed to combine 3 half-dose antihypertensive agents, an intermediate-dose statin, low-dose aspirin, and folic acid into a once per day polypill for primary and secondary prevention of cardiovascular disease. Based on epidemiological models, they estimated that daily use by individuals aged 55 years or older could reduce the incidence of MI and stroke by more than 80%.

In the 12 years since this report was published,3 versions of the polypill have been successfully tested in several phase 2 (safety) studies and a few modest-sized phase 3 (efficacy) trials. Collectively, these studies demonstrated that the polypill was well tolerated, achieved good adherence, and based on intermediate end points, such as reduction of blood pressure and low-density lipoprotein cholesterol level, is efficacious…

The 4 drugs in the current version of the polypill have long histories of safe use. Although all 4 are frequently prescribed in the United States, the US Food and Drug Administration (FDA) has not approved combining them in a single pill…

Although the polypill could produce substantial public health benefits, people in the United States are unlikely to find out anytime soon. This is because the pill’s price is so low (≤$1 per tablet) and the cost of the large clinical trials required for FDA approval is so high, it is unattractive to investors. The inventor’s dilemma is that creating a product that improves health is not enough; the product must also be able to generate a healthy return on investment. In the United States, the surest way to generate a healthy return on investment is to increase health care spending, not reduce it.

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“Negative Externality,” Splitting Checks, and Feeding Psychology

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If you have a great psychology book that you recommend, please let me know.  As frequent readers of this blog know, I am fascinated with psychology experiments.

In a recent blog from fivethirtyeight.com, the author tackles the question of whether people eat more when they know they are splitting a dinner check. Does it Make Sense to Split The Check at a Restaurant?

Here’s an excerpt:

In 2004, a study in The Economic Journal, a publication of the Royal Economic Society, …the researchers told four groups of diners (always three men and three women) to split the bill equally among them. They told another four groups to pay for what they had ordered. Lastly, they told two lucky groups that they would get their meals for free…

Those who were getting a free meal spent the most … Those who were splitting the bill spent less, and those who were paying individually spent the least…

Any time you make a decision that affects someone else without considering how it might affect that person, whether positively or negatively, you create an externality — it’s basically a fancy way of saying “indirect effect.” There are positive externalities (e.g. when you decide to get a flu shot, other people benefit) and negative externalities (e.g. when you decide to fart, other people suffer).

The unscrupulous diner’s dilemma reveals how negative externalities — and even the mere threat of negative externalities — affect our behavior. Participants in the bill-splitting experiment expected the others to order more, so they tried to maximize what they could get out of the situation by ordering more themselves.

Bottomline: It is fascinating to me how something as simple as splitting a bill may encourage someone to order a lot more.

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Near Fairy Falls, YW

How the Trans-Pacific Partnership Could Affect Health Outcomes

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Generally, trade agreements are not something I scrutinize and typically have little to do with the medical field.  Recently, I was surprised to learn that the Trans-Pacific Partnership (TPP) has language in its intellectual property chapter that could impact the lives of millions (A Kapczynski. NEJM 2015; 373: 201-3).  The background for this story is that pharmaceutical companies want to have patent protection for their medications for as long as possible.  This has a substantial impact on pricing.  “For example, patents increase the annual cost of antiretroviral therapy from around $100 per person to $10,000 per person.”

Some countries, like India, have undermined patent protections.  “India allows patents on new drugs but not on new uses of old drugs or new forms of known drugs that do not increase therapeutic efficacy.”  Other countries have been following India’s lead.  Even in the U.S., there are efforts to decrease data exclusivity, which prevents regulatory agencies like the FDA from registering a generic version of a drug.

“President Barack Obama’s fiscal year 2016 budget proposes rolling back the data exclusivity period for biologic drugs in the United States to 7 years from 12 years, yielding a projected savings of more than $4 billion over the next decade. In the TPP negotiations, however, the United States is proposing a 12-year term of exclusivity.”

Other potential concerns include both the elimination of a provision to use “competitive market-derived prices” and the potential for promoting foreign companies to sue TPP countries for millions of dollars in damages due to loss of profits.

Currently there are escalating drug prices, both with innovative new medications and well-established treatments. Even lifesaving cures are being rationed in the United States.  While the TPP has not been finalized, there are provisions that could limit the United States  from regulating “critical aspects of health policy for years to come.”

Related blog posts:

Cascade Canyon, Grand Tetons

Cascade Canyon, Grand Tetons

 

 

Understanding the Problem Physicians Have With Retail Clinics

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Two articles highlight the upside and downside of retail clinics.

  • Iglehart JK. NEJM 2015; 301-3
  • Chang JE et al. NEJM 2015; 382-8

Currently, there are ~1900 retail clinics with four main ‘players:’ CVS, Walgreens, Kroger, and Target.  However, Target has recently made a deal with CVS and Walmart is expanding into retail clinics as well.  Almost all of these clinics accept private insurance and medicare; growing numbers accept medicaid too.

Retail clinics offer a limited scope of care and typically are staffed by midlevel providers (nurse practitioners or physician assistants).  In contrast, urgent cares offer more complex services and typically are staffed by physicians.

Upside:

  • For consumers, the key advantages of retail clinics: lower costs with transparent pricing, convenience due to extended hours and locations, and often short wait times.

Downside:

  • Potential disruption in longitudinal care (“medical home”)

What about quality?

  • “Research has not found that retail clinics deliver poor quality care, overprescribe antibiotics, or adversely impact delivery of preventive care.”

Do Retail Clinics Enhance Access?

  • Yes but these clinics are disproportionately located in areas with relatively high income.  Nevertheless, “approximately 61% of retail-clinic visits and 37% of urgent care visits involve patients without a primary care provider.”

Patient navigation:

  • “One study …showed that patients did properly self-triage, with more than 88% of retail-clinic episodes resolved in one visit. Another study showed that 2.3% of retail-clinic patients were triaged to an emergency department or physician’s office.”

Why Would Physicians Oppose These Retail Clinics?

  • While primary care organizations have raised concerns about quality and continuity of care, a basic economic issue is likely at work as well.  “The current reimbursement system renders simple acute health problems high-margin work that can offset losses from treating more complex problems.“

Bottomline: Retail clinics are filling a need for many patients in terms of cost and convenience for simple acute problems.

Related blog post: AAP -Behind the Scenes (Part 1)

Leek's Marina, Grand Tetons

Leek’s Marina, Grand Tetons

Would Medical Marijuana Meet the Threshold for FDA Approval?

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For most conditions –the answer is no.  A recent study was reviewed by several media outlets including the LA Times.  Here is an excerpt:

A comprehensive review of dozens of clinical trials that have tested medical marijuana for 10 conditions finds that there’s very little reliable evidence to support the drug’s use. The review, by an international team of researchers, was published Tuesday in the Journal of the American Medical Assn.

Patients who use medical marijuana to treat chronic neuropathic pain or cancer pain would probably have the least to fear from an FDA review. The JAMA study considered 28 studies involving 2,454 patients and concluded that there was “moderate-quality evidence” from at least a dozen studies showing that cannabinoids – chemicals in marijuana that produce pharmacologic effects inside the body – reduced pain in such patients by modest amounts….

The other condition for which medical marijuana proved useful was muscle spasticity in people with multiple sclerosis. After assessing 14 studies with 2,280 patients, the JAMA authors determined there was “moderate-quality evidence” to support its use in these patients, although many of the studies reported improvements that weren’t quite big enough to qualify as statistically significant…

One of the things the studies showed most clearly is that people who use medical marijuana had a “much greater risk” of side effects, including serious problems like kidney, liver and psychiatric disorders. The most common adverse effects included dizziness, confusion and disorientation,  according to the JAMA report…

The authors, from the Yale University School of Medicine, lamented the fact that state approval of medical marijuana had been based on “low-quality scientific evidence, anecdotal reports, individual testimonials, legislative initiatives, and public opinion.”

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Zoo Atlanta

Zoo Atlanta

Genetically Modified Humans: Genome Editing 101

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In a review at last year’s NASPGHAN meeting, John Barnard gave a basic science review (Basic Science Year in Review -#NASPGHAN 2014 | gutsandgrowth) that touched on CRISPR-Cas9 for genome engineering (Cell 2014; 157: 1262-78).  Reading through a recent editorial (Lander ES. NEJM 2015; 373: 5-7), it seems that the potential for genome editing is not that far from landing into clinical use.

His points:

Genome editing holds great therapeutic promise…

  • “physicians might edit a patient’s immune cells to delete the CCR5 gene, conferring the resistance to HIV carried by the 1% of the U.S. population.”
  • “Editing blood stem cells might cure sickle cell anemia and hemophilia.”
  • Eliminate genes which increase the risk for Alzheimer’s, Huntingdon’s disease and heart attacks

Concerns:

  • “Genetically modified humans” and true “designer babies”
  • Technical issues to perform editing with precision.
  • Unanticipated effects with various edits. “We remain terrible at predicting the consequences of even simple genetic modification.”
  • Who decides?  Future generations cannot consent to their modification.
  • Is it morally right? “Would the ‘best’ genomes go to the most privileged?”

In the U.S., genome editing would not garner approval from FDA or NIH in the near future. But, given the advancing technical capabilities, it is not too early to begin the discussion about genome editing.  At the very least, this technology should spurn a couple great sci-fi movies.

Take-home point: “Authorizing scientists to make permanent changes to the DNA of our species is a decision that should require broad societal understanding and consent…We should exercise great caution before we rewrite” the human genome.

Zoo Atlanta (Kinda looks like a genetically-modified giraffe)

Zoo Atlanta (Kinda looks like a genetically-modified giraffe)

Not Thirsty for Water

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As noted in several previous posts (see below), many kids (and adults) would likely benefit from increased water consumption.  The pervasiveness of this problem was recently discussed in a recent (June 11th) USA Today article (“Researchers to kids: drink more water”), though experts disagree on whether mild water deficits are detrimental.

Here’s an excerpt:

The study, published Thursday by the American Journal of Public Health, found 54.5% of children ages 6 to 19 inadequately hydrated, at least by the standard set in the study.

The findings, based on one-time urine samples from more than 4,000 children, do not mean most children are seriously dehydrated…

The researchers considered a child inadequately hydrated if the concentration reached a level other studies have linked to sluggish thinking and mood changes.

They found boys and black children were more likely than girls and children of other races to have highly concentrated urine…

But … some experts …say most people can judge their fluid needs by thirst alone – and that fluids can come from any drink and many foods…

The study showed 22% of children drank no water.

 

Not drinking enough water

 

 

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Point of Care -Mobile, Anywhere, Cheap EKGs

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Note:  This blog and author do not have any financial disclosures or receive any support from any companies.

Using a smartphone app, AliveCor has developed the technology to obtain a limited EKG (ECG) for a minimal cost; after an initial investment of $74.99, this technology can function similar to a standard EKG machine but only provides one lead (V1).

From the AliveCor website (thanks to Larry Saripkin for showing me this):

The FDA-cleared AliveCor Mobile ECG wirelessly communicates with the free AliveECG app, available in the U.S. App Store and Google Play Store. ECGs are stored in the app and on secure, encrypted servers that can be viewed anytime, anywhere. ECGs can also be printed or e-mailed directly from your smartphone or tablet, and you can grant access to your physician.

Do I have to attach the Mobile ECG to my smartphone or tablet? That is our recommendation, however, you may use the Mobile ECG within 12 inches of your smartphone or tablet if you’d like….

Simply rest it on your fingers or chest to record an ECG in just 30 seconds. Know right away when your ECG is normal and if atrial fibrillation is detected.

Potential Uses:

  • Detect atrial fibrillation
  • Correlate symptoms like palpitations and shortness of breath
  • Accurately assess heart rate
  • ?Assess for QT interval -this could be particularly useful to pediatric gastroenterologists

While many of the uses may be self-evident, the website offers ECG review by a U.S. board-certified Cardiologist, with an average turnaround time of 24 hours. The current price of this service is $12.

Bottomline: This is another example of how new technology improves clinical information and at the same time should be less expensive and more timely.

Related blog posts:

Disclaimer: These blog posts are for educational purposes only. Specific dosing of medications/diets (along with potential adverse effects) and use of new technology should be confirmed by prescribing physician/nutritionist.  This content is not a substitute for medical advice, diagnosis or treatment provided by a qualified healthcare provider. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a condition.

Sign at Children's Healthcare of Atlanta

Sign at Children’s Healthcare of Atlanta

Critique of the 21st Century Cures Act

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The most compelling article (Avorn J, Kesselheim AS. NEJM 2015; 372: 2473-5) in a recent edition of the NEJM delved into the 21st Century Cures Act which was recently introduced in the U.S. House of Representatives; it was approved 51 to 0 in committee but continues to be debated.

One of the underlying premises of the bill is accelerate approval for new products. Key features:

  1. Increase in National Institutes of Health (NIH) of about 3% per year for 3 years. And, additional $2 billion per year for 5 years to create an “NIH Innovation Fund”
  2. Instructs FDA to consider nontraditional study designs for clinical trials.  This is aimed at shorter, smaller and less expensive studies.  This could allow FDA to rely on “observational studies” and “clinical experience.”
  3. The bill encourages the FDA to rely more on surrogate end points
  4. The bill would allow informed consent to be bypassed if the “proposed testing poses no more than minimal risk.”

Critiques for each point, point by point:

1. The funding increases largely counterbalance stagnating funds at the NIH secondary to sequestration and budget cuts.

2.  The premise that the FDA is inefficient is not accurate.

  • “A third of new drugs are currently approved on the basis of a single pivotal trial” with a median of 760 patients.
  • Most drugs are approved based on studies with a duration of 6 months or less, even medications taken for a lifetime.
  • Evaluation of nearly all new drug applications is completed within 6 to 10 months.

3.  Surrogate markers often overestimate the potential benefit of medications.  The FDA “already uses surrogate end points in about half of new drug approvals.” Specific examples:

  • Bevacizumab has been shown to delay tumor progression in breast cancer “but was shown not to benefit patients.
  • Rosiglitazone “lowered glycated hemoglobin levels in patients with diabetes even as it increased their risk of myocardial infarction.”
  • One new tuberculosis drug improved bacterial counts in the sputum but “the treatment group had a death rate four times that in the comparison group.”

4.  Informed consent has been “sacrosanct, with exceptions made only when consent is impossible or contrary to a patient’s best interests.”  With this new proposal, “it is not clear who gets to determine whether a given trial of a new drug poses “minimal risk.”

Bottomline (from authors): The 21st Century Cures Act’s call for increased NIH funding may prove to be its most useful component.  But political forces…could lead to the approval of drugs and devices that are less safe or effective than existing criteria would permit.”

Audio interview with Jerry Avorn: nej.md/1TPy6Ta

Some pictures from yesterday’s Peachtree Road Race:

Coveted T-shirt -2015 Edition

Coveted T-shirt -2015 Edition

Screen Shot 2015-07-04 at 6.34.03 PM

Rainy Day for a 10K

Largest 10K in U.S

Largest 10K in the World

Mobile Technology Medicine Improves Bystander CPR

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A recent study (Ringh M, et al. NEJM 2015; 372: 2316-25) shows that the ubiquitous nature of mobile phones/smartphones can lead to improved rates of bystander CPR.

The authors conducted a blinded, randomized controlled trial in Stockholm (2012-2013) using a mobile-phone positioning system.   The intervention group had trained bystanders dispatched who were within 500 meters of individuals with out-of-hospital cardiac arrest.  The control group received standard care.  The primary outcome was bystander-initiated CPR before the arrival of ambulance, fire, and police services.

Key finding: With a network of 9828 trained volunteers, the intervention group had CRP initiated in 62% (188 of 305) compared with 48% for the control group (172 of 360)

The associated editorial (pg 2349-50) notes that in the U.S., every hour there are 38 people who have out-of-hospital cardiac arrest and fewer than 1 of 10 survive.  They note they timely CPR improves survival rate.  In a previous study, provision of CPR prior to EMS arrival increased survival from 4.0% to 10.5%.  Besides technological limitations in the U.S., another potential barrier for trained bystanders would be allowing access to their location at all times and the “fear of being sued if they do not respond to a call.”

Bottomline: While there are barriers to be overcome, this is another example of reimagining the uses of new technology and developing a truly interconnected health network.

Related blog post: Can Apple Make Research Cool? | gutsandgrowth

Dungeness, Cumberland Island

Dungeness, Cumberland Island