Comparative Effectiveness Compare and Contrast

Since Sen. Max Baucus introduced his latest legislative attempt to create a national center on comparative clinical effectiveness research, we’ve had some time (OK, OK, a week—it is summer, after all) to dig into the details.

With the help of our colleagues over at “The Pink Sheet,” we’ve put together a list of some of the key differences between the Baucus bill (S 3408) and previous comparative effectiveness legislation—including language in the senator’s own Medicare Part D price negotiation bill from 2007.


So here’s a little compare and contrast, as reported in this week’s issue of The Pink Sheet.”

Organizational structure: Baucus would create the “Health Care Comparative Effectiveness Research Institute” as an independent, public-private entity. Past efforts had the Agency for Healthcare Research & Quality as a central player: The CHAMP Act would have established a center inside AHRQ, and Rep. Tom Allen (D-Maine)'s bill would have established a trust fund through the quasi-government agency.

Who sets the agenda?: Research priorities would be determined by the center itself. That’s a change from the comparative effectiveness language in Baucus’ Medicare Part D price negotiation bill, under which HHS would set the research agenda. But the government would have some influence over what would be studied: the HHS secretary and NIH director would sit on the governing board.

Money, money, money: Baucus calls for appropriations of $5 million in 2009, $25 million in 2010 and $75 million in 2011. Starting in the fourth year, annual contributions would be made from the Medicare Trust Fund ($1 per beneficiary per year), revenues generated by a fee on private health insurance policies ($1 per insured person per year); and general revenues ($75 million a year). Funding would increase to $300 million a year by the year 2013, and all funding would sunset after 10 years.

By comparison, the CHAMP Act set government appropriation levels at $90 million, $100 million and $110 million during the first three years, but was not as direct in setting levels for private participation. The bill said that the private sector contribute beginning in the fourth year to bring the total trust fund amount of $375 million.

And then there’s the billion-dollar question for industry….

How will the research be used?: Baucus does not offer any specific guidance on how the information can or cannot be used by private or public payors. That’s a big change from the price negotiation bill, which clearly stated that “authorizing consideration of comparative clinical effectiveness studies in developing and reviewing formularies under the Medicare prescription drug program.”

Preserving the Right to Advertise—No Matter How Dumb it May Be

James Madison's Legacy?

Score another one for the lobbyists at Big Pharma and their allies on Madison Avenue: the House is poised to join the Senate in passing legislation that will put new restrictions on direct-to-consumer advertising—but without putting any moratorium on the right to advertise new products.

The House followed the Senate in bowing to concerns that giving FDA the explicit authority to prohibit DTC ads for new products raises significant Constitutional issues. So, like the Senate, the House bill will now move forward with language allowing FDA to preclear ads, to require disclaimers to prevent false or misleading promotions, and--perhaps most significantly—to levy fines for ads it deems violative.

But the moratorium idea—initially supported by heavyweights like Senator Ted Kennedy and Representative Henry Waxman—is officially dead.

Am I the only one who doesn’t see what the fuss is about?

Don’t get me wrong. We here at the IN VIVO Blog are HUGE fans of the First Amendment.

I just think this ship has already sailed. FDA may not be getting the authority to prohibit DTC for new products, but does anyone in industry seriously expect to be running massive TV campaigns for new drugs again any time soon? Why would they want to?

The Pharmaceutical Research & Manufacturers of America has already conceded the principle behind the moratorium proposals. The association’s voluntary DTC code states that, “in order to foster responsible communication between patients and health care professionals, companies should spend an appropriate amount of time to educate health professionals about a new medicine or a new therapeutic indication before commencing the first DTC advertising campaign.”

The PhRMA code does not specify a minimum waiting period. A one-size-fits-all policy would keep patients from learning important medical information for products that can be safely advertised, PhRMA says. (Oh, and you will be glad to hear the code is working just great. At least PhRMA says it is.)

At first glance, it is easy to understand why Big Pharma would still resist legislative change. After all, a three-year moratorium (as proposed initially in the House bill) enacted by Congress is a lot stricter than the voluntary code adopted by PhRMA.

Except that there really isn’t a difference. The three-year moratorium is the maximum that FDA could require. The minimum would be no waiting period at all for new drugs where FDA saw no issues with immediate DTC.

Plenty of people worry—with good reason—that FDA would err on the side of caution and limit DTC routinely, and presumably put the maximum limit on as often as possible. Sponsors, in effect, would have the burden of proving to FDA that ads would do more good than harm.

The thing is, that sounds to me like exactly the situation industry is in today. FDA may not have the explicit authority to prohibit DTC for new drugs, but they have asked for and received “voluntary” commitments by manufacturers not to advertise as a condition for approval. Sponsors could just to ignore those commitments and FDA would probably be powerless to stop them—but anyone who does that better be ready for the backlash.

And it doesn't take a broken commitment to trigger a backlash.

When an FDA advisory committee recently met to discuss the safety of erythropoiesis stimulating agents in treating cancer patients, there was palpable anger on the committee about Johnson & Johnson’s advertising of Procrit. Committee members felt that J&J's commericials implied a quality of life benefit not found in product labeling. There is no way to prove it, but my hunch is the committee would not have been as tough in its recommendations to restrict ESA labeling if they weren’t so concerned about J&J’s ads.

Then there are the broader implications of the FDA legislation itself. The DTC moratorium may be gone, but the new law will still give FDA a much stronger hand to put restrictions on the roll-out of new products. The era of the billion-dollar blockbuster launch may not be over, but those products are already far rarer than they were, and the new law will make them rarer still.

Far more common will be slow builds, where products spend a year or two on the market in limited use. Only when FDA and the sponsor agree the safety profile allows for it will products break out into broad patient populations.

So why would anyone want to run big TV campaigns for new drugs right after they reach the market anyway?

One way or the other, sponsors need to be prepared to prove that their ads do more good than harm. FDA may not have the authority to demand proof, but the agency—or frustrated members of Congress—can still put advertisers in the hot seat any time they want.

The BIO Perspective: It Out-PhRMA's PhRMA

I emailed Blog-colleague Ramsey Baghdadi last week to agree completely with his May 11 post about the security around this year's BIO event. (Even those of us who preregistered were similarly routed 3/4 around the center, by the way...) And I agree with him that some of the sessions were surprisingly more content driven than in the past: for this meeting I always wonder whether it's more presumptuous to expect to hear nothing new at the show, or to expect to hear something of merit. The 2007 edition appeared to be fine fodder for the freelance trade press, certainly, judging from the number of surprisingly pithy story pitches in my email afterward.

But bio has in many ways ceded its claim to be hoisting the banner of innovation, and that's unfortunate. I heard second hand that one biotech industry rep -- a former PhRMA intimate -- had commented at the meeting that "BIO is more PhRMA that PhRMA ever was." With respect to follow-on biologics, for example, its initial stance has been to stall, saying Congress shouldn't link it to PDUFA reauthorization because it was too scientifically complex to resolve in that timeframe, and besides, that the health care system should not expect to see signficant cost savings from FOBs.

Or as one ex-BIO staffer said to me, "Blocking innovation is what PhRMA does, like when it tried to stop Hatch-Waxman." Where previous bio leadership would take the heat from big companies (in part to be seen as an alternative voice to PhRMA), advocacy on FDA policies is now set by the larger companies' Washington offices. Carl Feldbaum preached the importance of political neutrality, but the partisan, hooked-into-the-White-House Greenwood team hadn't planned for a Democratic win in '06, and has to build those bridges.

That said, there's no doubt that the spirit of innovation lives on in the hearts and minds of companies, investors, and other biotech stakeholders. And it's not even that BIO's voice is the wrong voice. It's just not -- no longer -- a voice of innovation. The Emerging Companies Section -- a notion integral to the merger between IBA and the smaller ABC that created BIO way back in 1993 -- appears to be fading away. In light of its policy positions, when the organization in its role of external advocate speaks of risk-taking, it rings hollow.

Congress Is Still Open to Drug Incentives

While neither of the anti-infective incentives in the Senate FDARA bill we wrote about earlier this week appears to create a niche for a blockbuster commercial product, together the incentives show that there is still room for pharma advocates to negotiate for incentives with the Democratic Congress.

That’s an important point as potential biogenerics legislation hangs around the fringes of the progressing user fee/drug safety bill (S 1082, the Food & Drug Administration Revitalization Act).

Democratic and Republican staffers involved in the follow-on biologics debate have reported good progress on the approval pathway and safety issues for follow-on biologics. They have said publicly that they expect more difficulty around the incentive discussions.

If history is any guide, the ability of the existing innovators in the biologics category (primarily Amgen, Biogen-Idec, Genentech, Genzyme and J&J) to carve out protections for their products will determine whether follow-on biologics is added as a last-minute part of the PDUFA/drug safety package this year.

That’s how Waxman-Hatch was passed in 1984 (when Pfizer and J&J cut deals to protect some of their major in-line products) and that’s what it will take to get a follow-on biologics bill this session.