Tuesday, October 25, 2011

Farewell to Xigris--Counting the Lessons

One of my most faithful readers sent me a link to David E. Williams blogging on the Health Business Blog:

Williams in turn comments on news that Eli Lilly has withdrawn its drug Xigris (recombinant human activated protein C) from the market after a new, major study failed to show any benefit in survival from sepsis:

The bulk of Williams' post is actually a reprisal of an old post, but it's still very timely, and for readers of this blog, provides a view of physician responsibility for drug industry marketing excesses from a vantage point outside of medicine.

I told the Xigris story in HOOKED as of 2006 or so. Basically Lilly gets credit for really trying to come up with a novel compound that attacked disease (life-threatening infection or sepsis) in a novel way. The sad news was that the initial trial showed that Xigris was only occasionally effective and also carried major bleeding risks.

The part of the Xigris story that especially caught my attention was how some of my colleagues in bioethics were caught up in the company's PR campaign without apparently realizing it--or else taking the money and not caring. As one prong of the marketing strategy, Lilly decided that since Xigris cost so much, and since so few ICUs were purchasing it (since the studies had been so equivocal), then there must be rationing of life-saving treatment going on. Of course one solution would have been to lower the price, but perish the thought. So Lilly instead forked over $1.8M to fund an "ethical" study of rationing in the ICU, with the intent of bringing pressure to bear on recalcitrant units with the dreaded "R word."

The part of the story that I did not cover in HOOKED, as Williams reminds us, was actually addressed in a 2006 commentary in the New England Journal (subscription required) by Eichacker and colleagues. Having managed to get the FDA to approve Xigris despite iffy data of efficacy and safety, Lilly bankrolled a big PR firm to do three things--set up the rationing "ethics" inquiry, and get major medical societies to write guidelines for sepsis care that included the use of Xigris (by funding the guideline panels and making sure that numerous docs with Lilly money in their pockets served on the panels). The third thing however was what made Eichacker and company worried. It was Lilly's subsequent effort to lobby the organizations that create quality indicators for hospitals and insurers to include those guidelines in their quality measurements. That is, if an ICU did not use Xigris, because they deemed it insufficiently useful and overly dangerous (a reasonable evidence-based position at the time), the hospital might get a lower score for quality of care and then have problems with insurance reimbursement as well as the bad publicity. Eichacker et al. very reasonably said this was a blatant hijacking of these quality indicators for commercial purposes.

I have commented numerous times on Kalman Applbaum's concept of controlling the drug channels. Lilly did this beautifully, gathering in its hot little hands all the threads that controlled the way hospitals were likely to use Xigris. Why bother sending drug reps into thousands of doctors' offices if you can buy off the people who write the guidelines and the people who ding the hospitals for bad quality of care?

So now we find out, at this late date, what many suspected from the start--that even the small degree of benefit for Xigris, that was seen in the initial study and that earned FDA approval, was probably a fluke. Farewell to yet another overmarketed and dangerous drug--though too bad that Lilly did not go back into the laboratory and try to use the basic understanding of the disease mechanism to find a better successor.

Here are Williams's take-home messages for the industry and for physicians, worth repeating here:

Here’s some free advice to the different players in health care:

--Industry: Feel free to market your products and services aggressively, but don’t take things too far. If you do you’ll end up killing the goose that lays the golden eggs. No one will trust doctors, guidelines or journals anymore
--Physicians: Remember that pharma and device companies are not stupid. If they spend money supporting your research or sending you to conferences or sponsoring continuing medical education it’s because they expect to get a return on their investment. It’s awfully hard to remain objective in such instances. Your job is to adopt the best medical practices and put the patient first –sometimes that requires expensive new treatments and sometimes old, cheap standbys are better

Eichacker PQ, Natanson C, Danner RL. Surviving sepsis--practice guidelines, marketing campaigns, and Eli Lilly. New England Journal of Medicine 355:1640-42, 2006.

1 comment:

Vaporizer said...

One of my most loyal readers sent me a link to David E. Williams blog blog business health check.