Last week, the American College of Physicians (ACP), a 129,000-member group of internal medicine physicians, and second-largest doctors group in the US, called for increased FDA authority and  funding to help protect  consumers from the risks of newly-approved prescription drugs.  Their six recommendations were:

1) increased funding for FDA staff and technological capability to keep pace with the increased workload due to the number and scientific complexity of new products submitted for pre-approval, globalization, and emerging safety challenges.

2) increased FDA authority and capacity to regulate drugs manufactured outside the US;

3) expanded FDA authority and involvement in the design of clinical trials to better evaluate safety and efficacy, through longer trials with larger, more representative target populations;

4) a ban on clinical studies of ‘bundled’ drug products that reduce access to drugs;

5) Improvements that increase  reporting of adverse events by doctors and others; and

6) limits on direct-to-consumer advertising in the first 2 years a drug is on the market.  

Increased FDA funding:

The ACP report notes that FDA’s “ability to approve and monitor new drugs has been compromised by chronic underfunding, limited regulatory authority, and insufficient organizational structure.” ACP recommends that FDA funding is increased, to improve their “ability to approve and monitor prescription drugs….”

 Regulating drug manufacturing overseas:

The ACP should be praised for bringing attention to severe under resourcing at FDA, particularly as it affects the Agency’s ability to ensure the safety of drugs manufactured overseas. Today’s globalized pharmaceutical supply chain has rapidly outgrown FDAs capacity, and FDA is not able to inspect foreign sites with any meaningful frequency. A 2008 GAO study found it would take FDA 13 years to inspect each foreign manufacturing establishment once, while domestic sites are inspected on average every 2.7 years.

 ACP points out that a provision for increased foreign inspections were included in a bill (H.R.759) introduced by Reps. Dingell, Pallone and Stupak in January this year. A similar bill (S.882) championed by the late Senator Kennedy and Senator Grassley also seeks to increase foreign site inspections by FDA. Both bills establish new industry user fees to pay for this expanded oversight, but also require annual increases in other appropriations to ensure sustainability. ACP importantly indicates that both types of financial support are needed, and mentions a number of other key provisions in the House bill, including a requirement for dedicated foreign inspection staff.

Facilitating increased physician reporting of adverse events:

The ACP also recommends FDA pursue efforts to “educate physicians on how and when to report an event that is potentially drug-related.” They also proposed streamlining the reporting systems and ensuring anonymity to “facilitate reporting by health professionals.”

DTC advertising of new drugs:

The report acknowledges that direct-to-consumer (DTC) advertising can “dramatically increase [use] of a new drug and … may expose large numbers of people to a drug with undocumented safety concerns.”

The best example of this concerns was seen in the  rapid use of the  pain-killer Vioxx upon hitting the market. The aggressive DTC advertising and other promotional activities  by manufacturer Merck lead to Vioxx’s use by over 20 million consumers, which then lead to  88,000-139,000 cardiac events, and  an estimated 35,000-55,000 deaths.  Adverse reactions and safety concerns arose with the  drugs Zyprexa and Bextra, among many others 

To address this concern, ACP recommended that FDA ‘limit’ the DTC advertising of newly approved prescription drugs, and require that labels and ads indicate that data related to the new drug’s “risks and benefits … are less extensive than those [for older] products…”

 Prohibiting clinical trials of ‘bundled’ products:

In addition, ACP also makes a recommendation that would help FDA avoid placing itself in the position of helping drug manufacturers introduce ‘bundled’ or combination drug products designed to protect a drug from generic competitors. 

For example, the report describes how, in 2005, the drug manufacturer “Pfizer submitted plans to the FDA to begin conducting large trials to test the cholesterol drug torcetrapib in combination with the popular and widely used statin Lipitor.”  By allowing clinical trials of the ‘combination drug’ rather than just torcetrapib alone, approval of the new combination drug product would insulate Lipitor from competition. This then puts FDA, in approving the study design, in the awkward position of helping the drug manufacturer avoid anti-trust prohibitions, the report said.

This concern is similar to the claims in the PAL member lawsuit on the drug Norvir, where drug manufacturer Abbott Labs bundle their HIV protease inhibitor cocktail drug Norvir in a new bundled-product-drug Kaletra, in order to increase market share.

ACP recommends that FDA not approve clinical trials which seem to be designed to ‘bundle’ a new drug with an existing brand name drug, and thus perpetuate the patent-protected sales of the new combination product.

To read the full report, visit http://www.acponline.org/advocacy/where_we_stand/policy/fda.pdf

Yesterday, Democratic presidential contender John Edwards announced a set of proposals to “Stop Misleading Drug Marketing By Standing Up To Drug Companies.”

We’re glad to see these proposals, not necessarily for their specifics as such (more on that later), but rather for their “diagnosis,” if you will. Edwards is correctly pointing the finger at drug advertising as a major factor in runaway drug spending and inappropriate prescribing. The statement on his website points to the explosion of spending on drug ads since the FDA relaxed the rules for such ads in 1997, reiterates that drug companies spend roughly twice as much on marketing and administration as they do on research and development, and highlights the role that drug ads play in “promoting ineffective and even dangerous drugs” (sing Zelnorm as an example — which we’ve written about here before: Zelnorm: A Case Study in why drug advertising is a bad idea). Finally, he lays a good chunk of the blame were it belongs: On the FDA, for failing to review drug ads in a timely manner, and on the pharmaceutical industry’s massive spending on lobbying and campaign contributions, producing a Congress that lacks the gumption to pass real and significant reform of how drugs are tested, approved, marketed and paid for in the U.S.

Here’s what his campaign website says he proposes to do, and our thoughts on each proposal

Proposal #1:

Delay New Ads to Put Safety First: Often, serious safety issues appear only after a drug has hit the market. Edwards will institute a two-year delay on consumer advertising of all new drugs, as recommended by the Institute of Medicine and the American Medical Association. A delay will ensure that well-informed doctors – not high-paid advertising consultants – drive prescriptions in the early phases before Americans know the full effects of new drugs.

Our thoughts: The “two year moratorium” has been batted around since Merck’s voluntary withdrawal of Vioxx back at the end of 2004. Most recently, this was briefly proposed as a provision in the FDA Amendments Act of 2007 (FDAAA – as in “open wide and say Fdaaaaaaa….”), but taken out, after the industry lobbied heavily against it and made implicit and sometimes explicit threats to sue to block it on the grounds that it would violate drug companies’ free speech rights. PhRMA, the drug industry’s lobbying group, included in its ” Guiding Principles on Direct to Consumer Advertisements About Prescription Medicines” (for which PhRMA received one of PAL’s coveted Bitter Pill Awards, the “The Fox Guarding the Hen House Award : For Pushing Toothless Voluntary Guidelines on Drug Advertising”) a provision calling on signatory companies to:

“spend an appropriate [unspecified] amount of time to educate health professionals about a new medicine or a new therapeutic indication before commencing the first DTC advertising campaign.”

In other words, even PhRMA supported a delay between the introduction of a new drug and when ads begin appearing on TV — but they of course wanted it to be voluntary.

What would such a delay do? Such delays are premised on the idea that the reality of new drugs — side effects, risks, etc — doesn’t become clear until several years after the drug has been on the market. The clinical trials which drug companies submit to the FDA test the drug on, at most, a few thousand people. Unusual risks and side effects, or those that show up only after prolonged use, either don’t show up in those trials or fly below the radar. Supporters of drug ad moratoria presume that more of those longer-term or rarer side effects and risks will be apparent after the moratorium ends, than if drug ads started right away. That is likely true, although two years may not be enough. If drug ads are delayed, patients won’t be seeing ads on TV for a brand-spanking-new drug the week it comes on the market and thus not crowding their doctors’ offices demanding a prescription. The notion is that doctors will have two years to come to a calm, independent conclusion about the drug — and then they’ll be better prepared to deal with patients’ demands for the Wonder Drug they just saw on TV.

But this presumes too much. What will be happening in those two years? Those legendary perky young attractive drug salespeople will be descending on doctors’ offices to preach about the wonders of the new drug to doctors. Medical journal articles written or ghostwritten by doctors on the take from the drug company will appear, lauding the new drug. “Thought leaders,” physicians identified by the company as particularly influential, will get paid to be “guest speakers” at conferences and dinners to talk about how great the drug is.

In other words, the same thing that goes on now in doctors’ offices will continue to go on, skewing doctors’ impressions of new drugs, and convincing them to prescribe them to their patients, even if it’s more expensive and no better. There’s nothing to guarantee that a doctor will to a more independent or more thoughtful conclusion about a new drug just because there was no ad on TV in the first two years.

While it’s true that evidence about side effects and risks, and about the drug’s true effectiveness, may come to light in the intervening two years, such a delay in and of itself will not do much to change the landscape of drug advertising. A drug can be hyped through clever ads whether it’s been on the market for a day or a decade. A delay presumes too much by concluding that ads for drugs have any place in our health care system — a conclusion that every other country besides the US and New Zealand has rejected.

Proposal #2:

Get Control with Real Oversight of Advertising: Edwards will give the Food and Drug Administration real power to prevent misleading drug ads by requiring the agency’s approval before drug companies can launch major ad campaigns. He will also increase the penalties for drug companies that violate truth-in-advertising laws.

The aforementioned FDA Amendments Act of 2007 gave the FDA for the first time the power to charge fees for drug companies that submit their drug ads for “pre-broadcast approval.” However, it didn’t go so far as to require that drug companies submit their ads before they air. As long as submitting ads before broadcast is “voluntary,” drug companies will be able to run ads that violate the FDA’s standards.

The FDAAA also gave the FDA the power to impose fines on drug companies that violate these standards (before, all the FDA could do was send the company a letter asking them to stop running the ad, and usually these letters came months after the ad had stopped running). So even if a drug company doesn’t submit an ad for “pre-broadcast approval,” the FDA theoretically now has the power to do something about it (levy a fine). It remains to be seen whether the FDA actually will ever use this power to levy a fine, and whether it will back down the company that gets fined raises a stink about it. As far as Edwards’ proposal to “increase the penalties,” there’s not enough detail there to comment on it. Except to say that the penalties allowed for under the FDAAA are modest — up to $250,000 for each violative ad, but not exceeding $500,000 for the same company in three years. And the key words here are “up to,” as we’ve said here before.

Proposal #3:

Require “Whole Truth” Disclosures: Edwards will improve drug makers’ disclosures to the public, requiring companies to tell the public the whole truth about side effects and how effective drugs are against placebos and existing alternatives. As a result, drug companies will no longer be able to advertise costly “me-too” drugs without disclosing the existence of less costly alternatives. He will also require drug companies to disclose foreseeable side effects from implants of medical devices, which are not disclosed today.

This gets to one of the main problems with how drugs are evaluated in the United States – the FDA only requires that a drug company show that its new drug is better than a placebo – in other words, better than nothing. There’s no requirement that a drug company test their new drug against other drugs treating the same thing, or that they tell you how their drug stacks up against competitors. It is a system like this that allows a drug like Nexium, which is no better than its predecessor Prilosec, to rack up $4.6 billion in 2006 sales. A huge percentage of new drugs in the past ten years have been so-called “me too” drugs — drugs that treat the same thing in the same way (mechanism of action) as other drugs currently on the market. Most of the time, there’s no meaningful difference between the various drugs. Yet this is the stuff that billion-dollar blockbuster drugs are made of.

It’s not clear from this proposal exactly what Edwards proposes to require. The next proposal offers a little more detail:

Proposal #4:

Help Doctors Make Decisions Based on Evidence, Not Ads: Edwards will establish a non-profit or public organization – possibly within the Institute of Medicine – to research the best methods of providing care, drawing upon data from Medicare and the Health Care Markets and medical experts from across the nation. The center will perform head-to-head testing of drugs, as well as devices, to see which work best for specific conditions and populations. It will quickly and widely disseminate its unbiased, scientific findings to physicians and patients. In addition, the FDA will require drug companies to conduct head-to-head testing prior to approving new drugs.

Head-to-head testing of drugs makes enormous sense and is one the main things missing in our current system. However, we should not be content to leave such testing to the drug companies themselves. Research has shown that studies head-to-head drug studies sponsored by one manufacturer tend to show that manufacturer’s drug in a more positive light (surprise!). Having an independent body do such testing makes sense. This is a central piece of what’s needed to make a shift to what’s being referred to these days as “evidence-based prescribing.”

Having the FDA require head-to-head testing as a condition of approval is intriguing, but again the proposal here is a little short on detail. Does this mean that the FDA would only approve drugs that perform better than others already on the market? Or does it mean that drugs that performed better than a placebo would still be approved, but would have to disclose that they didn’t perform better than other drugs.

In sum, Edwards’ proposals announced today offers some interesting and important ideas, and hopefully will contribute to a more vigorous debate in the presidential race about how to address these issues. Some of these proposals are not fully fleshed out, so fully evaluating them is not possible at this stage. Hopefully, more detailed proposals — from all the candidates — will be forthcoming. With health care continuing to rank second in most voters’ most pressing issues for the presidential candidates to address, and prescription drug costs contributing so significantly to the cost of health care, the candidates need to get specific about how they’ll rein in the worst excesses of the pharmaceutical industry.