ICEM 2014

ICEM 2014

Tintinalli Headlines & Holliman Assumes Presidency

On June 11, EPM Editor-in- Chief and renowned educator Judith Tintinalli took to the stage in Hong Kong to address…

The Medical Malpractice Rundown: A State-by-State Report Card

The Medical Malpractice Rundown: A State-by-State Report Card

When it comes to medical liability laws and culture, where you live matters.

Find out how your state stacks up against the other 49.

CT – Lowering Cost and Radiation

CT – Lowering Cost and Radiation

Medicare pays only about 20% of typical charges and radiation can be reduced by 90%.

The cost of a CT is actually quite nominal – the charge, however, is an entirely different matter. 

 Aftermath: The Night Shift Season 1 Finale Review

Aftermath: The Night Shift Season 1 Finale Review

At Loose Ends

It’s strange calling this a season finale, because it’s only been an 8-episode summer run, and nearly every episode has…

Doximity’s Next Trick: Connectivity at the Point of Care

Doximity’s Next Trick: Connectivity at the Point of Care

You’ve raised $81 million in investments and your physician membership now exceeds that of the AMA. What’s next?

If you're Doximity, it's time to dream big. 

Subcutaneous Insulin in DKA: Safe — But Not Better

Subcutaneous Insulin in DKA: Safe — But Not Better

Newer Isn't Always Better

Studies show that the benefits of subcutaneous insulin over old fashioned IV insulin are marginal at best.

A Return to (Lousy) Form: Episode 7 of The Night Shift

A Return to (Lousy) Form: Episode 7 of The Night Shift

Forks! Strippers! Guns!

Once again, our characters are responding to the (frankly unbelievable) events unfolding around them, rather than driving the action.

Oxygen is a Drug— Act Accordingly

Oxygen is a Drug— Act Accordingly

Understanding the dangers of indiscriminate oxygenation in the ED setting

As with many things in medicine, dogma seems to overpower the evidence in this arena. 

Oh Henry: A Sucker is Born Every Minute

Oh Henry: A Sucker is Born Every Minute

Pharmaceutical Ads, Government, and the Physician-Patient Relationship

Though it pains me to say it, this is one time where caveat emptor doesn’t apply. 


A Ray of Hope

A Ray of Hope

The Night Shift, episode 6

This was the first episode where it felt like the characters were driving the plot.

The Downside of the Upswing

The Downside of the Upswing

You should have cashed in big-time. 
But did you?

The last several years of returns have been among the best ever.

5 Things Your Patients Might Think After Watching ‘Code Black’

5 Things Your Patients Might Think After Watching ‘Code Black’

An inside view of the ED

Code Black provides a harrowing and enlightening window into the front lines of healthcare. 

Talking Points

Talking Points

Link your vision to action

As an ED leader, you must not only have a vision and plan, but you must communicate that vision effectively…

Toxic Liquid Nicotine

Toxic Liquid Nicotine

New FDA regulations proposed for E-cigs

Highly unregulated, the sale of toxic nicotine concoctions for e-cigarette refills pose a serious threat to children.

All Choked Up

All Choked Up

Best Practices for Battery Ingestion

A two-year-old presents at a clinic with persistent cough and neck discomfort and winds up in the ED.

Gag Order

Gag Order

New ruling prohibits would-be ACEP leaders from answering questions from non-ACEP publications.

Greg Henry seldom fails to deliver on a promise. But this time, it looks like it’s out of his control.

Lock the Gates!

Lock the Gates!

Board certification is vital in EM

Last month, Rick Bukata suggested that ACEP open its gates to non-boarded EPs. 
This would be an insult to EM…

AMA Meeting Highlights

AMA Meeting Highlights

Association Gives Nod to First EP President-elect

This June’s AMA Annual Meeting proved as eventful as ever, with one exciting twist that has the potential to impact…

The Storm Episode!

The Storm Episode!

Episode 5 of NBC's "The Night Shift"

It’s time for the passion that’s been building up between the two lead ED doctors for … the past few…

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Over the past few years, the emergency department treatment of septic patients has dramatically changed.  Much of this is due to the implementation of early goal directed therapy which emphasizes aggressive fluid resuscitation, early antibiotic initiation, vasopressors, and transfusion as needed.  Another innovation in the treatment of sepsis was the development of Xigris (recombinant human activated protein C or drotrecogin alfa) by Eli Lilly. This medication was approved with much controversy by the FDA in 2001 based on a single phase 3 randomized control study known as the PROWESS study, which showed overall survival benefits at 28 days with Xigris (Phase 3 studies compare the newer treatment or regimen with the pre-existing standard for treatment while phase 1 and 2 trials focus on the safety, kinetics, and dosages of the new treatment). The medication was approved in septic patients with minimum APACHE  II scores of  25 or  2 sepsis induced organ dysfunction.  There was, however, some controversy regarding the methodology of the study. Because of this, sales of Xigris did not meet expectations despite its approval. As a result  Eli Lilly hired a public relations firm to develop a marketing strategy to improve sales.

In recent years there has been a drive to put evidence-based intervention into “bundles” which are used to develop a protocol for physicians to follow. While this practice has a measureable effect on patient outcomes, it may have some harmful effects as well. One such effect is that some pharmaceutical companies may use these guidelines to promote their own products. Another effect of bundles is that they make it very easy to develop pay-for-performance packages in which compensation is dependent on compliance with the entire bundle.  In the authors’ opinion, Eli Lilly took advantage of such protocols to promote their drug Xigris in the sepsis protocol.

The marketing strategy consisted of “3 prongs” or phases.  The first phase involved establishing a Surviving Sepsis Campaign to raise physicians and the medical media’s awareness of sepsis. Second, Eli Lilly heightened the demand for Xigris by spreading the word that it was being rationed because of its high cost and physicians were being forced to decide who would receive it, and in turn, survive. The company provided a $1.8 million grant to establish the Values, Ethics, and Rationing in Critical Care (VERICC) task force to address the ethics behind rationing a potentially life threatening drug such as Xigris.  Eli Lilly also helped to fund the international panel of critical experts which gathered to develop the guidelines for management of sepsis which were published in Critical Care Medicine in 2004.  Lastly the Surviving Sepsis campaign was established to promote treatment of sepsis.  Lilly provided more than 90% of the funding for the first 2 phases of the campaign.

Even though many proponents will argue that despite their funding, Lilly did not influence the establishment of the sepsis guidelines, the fact that these recommendations are largely based on randomized controlled trials, automatically tends to favor newer treatments, such as Xigris, which need such trials for approval. Frequently already established practices such as antibiotics and fluid, are ranked less highly in such guidelines because they lack randomized controlled studies as established standards of care.
           
Furthermore, the original PROWESS study, also demonstrated an increased risk in bleeding (approximately 3.5% of patients) with Xigris which again manifest in the ADDRESS and RESOLVE studies. In the ENHANCE trial the risk was found to be even greater.  These results, however, were not included in the Surviving Sepsis Campaign Guidelines. In fact, the efficacy of rhAPC has not been prospectively shown even though the FDA had asked for further testing when Xigris was approved. While the PROWESS study showed a significant overall survival benefit at 28 days, the FDA only approved it for patients with APACHE scores greater than 25 even though the efficacy of Xigris has not been demonstrated in a prospective trial consisting of these patients.
 
In their final marketing phase, Eli Lily established the “Implementing the Surviving Sepsis Campaign” program in 2004 in order to create performance bundles based on  recommendations from the campaign guidelines. One branch of this bundle included a recommendation of Xigris even though the results of the ADDRESS and RESOLVE studies were not mentioned. These bundles are now being implemented internationally by the Society for Critical Care Medicine with funding from Eli Lilly.  It should be mentioned that the Infectious Diseases Society of America has declined to endorse the guidelines.

In conclusion , practice guidelines can be helpful in standardization of practices across diverse international health care settings improving patient outcomes.  To minimize bias and ulterior motives, pharmaceutical industry involvement in guideline development must be closely scrutinized.
 

 

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