What is pharma's problem, anyway?

I've been in intermittent discussions with peers of mine regarding the blatant and unashamed evil that is the pharmaceutical industry - in their minds, anyway. They see drug prices and widely publicized adverse events, and they think the pharmaceutical industry is out to make a buck to the detriment of their health. Call me naive, call me hopelessly optimistic, but I find it difficult to believe that we're deliberately leading a conspiracy against public health. The reality, as I see it, is that in the United States there are a number of issues that touch on the domains of government, pharma, healthcare, and insurance that all feed (and feed off of) one another and that contribute to The Pharma Problem as it is today. To wit:

• Governmental: Every New Drug Application that is sent to FDA is accompanied by a "user fee" per the Prescription Drug User Fee Act (PDUFA III). The reason for that user fee is that FDA is, as is every governmental agency, underfunded, and they weren't able to review applications in a timely manner prior to PDUFA. (More on why time is so important in the next bullet.) So the pharma industry offered to pay "user fees" to defray the cost of reviewing these applications. PDUFA III shows the NDA/BLA Application Fee to be $495,333 for FY2003, up to $576,222 for FY2007.


• Also governmental: Timing. Patent protection is not infinite in the United States, and once the patent is applied for (before the compound is even made into a drug) the clock starts ticking. Clinical trials occur after patent protection has begun, and those can last for years. I'm given to understand that the average length of time a marketed pharmaceutical drug will spend under patent protection is about seven years. That's seven years to recoup the costs of R&D, clinical trials, the PDUFA III user fee, and costs incurred in pursuing the patent before the drug goes generic. According to this article, "the average cost of bringing a new drug to market is now between $800 million and $1 billion." Quite a lot to recoup in seven years.


• Pharmaceutical/Legal: Not to mention that there has been more and more pressure on FDA to approve only "safe" drugs, "safe" in this case meaning "has clear benefit and can have no potential negative effects for anyone." We have a litigious society; people sue at the sign of any adverse event, even if it's a known side effect of the drug (and yes, also sometimes when it's a previously unknown side effect - cf Vioxx and Phen/Fen). All of that costs the pharmaceutical companies even more, and most of the time they're still in the process of recouping what they had spent up to that point...


• Pharmaceutical: ...so here we ring the bell and usher in direct-to-consumer advertising. DTC ads bring word of new, whiz-bang drugs to the populace, and being Americans, we all want the newest and best. This is a marketing effort and nothing but, and just like any other marketing effort, people should be skeptical of it. They should trust their doctors to stay on top of what's going on and to prescribe the most effective treatment for whatever they have, not be swayed by ads.


• Healthcare/Insurance: ...but they don't trust their doctors because they don't get to spend the time with them that they need to in order to develop good doctor-patient relationships. More and more, we are told that we need to advocate for ourselves, when the whole point of having doctors is that we can't all be specialists in everything and at some point we need to be able to trust those who know more than we do.


• Pharmaceutical/Governmental: And so we're back to the DTC ads. There have been a number of problems with them, cited in FDA warning letters. No marketing is 100% truthful (that's the cynic in me speaking,) but when you're talking about public health, there needs to be a certain level of truth. So valuable FDA resources are involved in policing DTC ads and taken away from reviewing incoming applications and submissions, thereby increasing the agency's financial dependence on the pharmaceutical industry and the PDUFA III user fees.


• Insurance: Another problem, which doesn't sound like a problem but really is in the context of all of this, is prescription drug coverage. Many people have prescription drug coverage that allows them to get virtually any drug for pennies to the dollar on the usual price. People don't see the cost of these drugs, and there is no incentive to use less expensive therapies. Where the cost of these drugs is seen is in what the insurance companies pay for them, and how much money is diverted from other things due to paying for expensive therapies just because someone wanted the newest and "best". Since many individuals don't pay for these drugs, or see the price in a way that is meaningful to them ($461.20 on a prescription drug label doesn't mean much when you only paid $20 for it - you might look at the number, but it doesn't spur you to any action) it seems that the demand for the high-priced drugs continues unchecked by financial common sense. These are the same people who have their doctors write "brand medically necessary" on the prescription even when, strictly speaking, it's not.


• Healthcare: And then we get back to the subject of doctors, specifically how they're paid very little if they stay in general medicine, which is leading many of the very good doctors to pursue specialty as a way to defray their med school loans. They are taught to rely on tests and on action as opposed to inaction, and to avoid malpractice suits at all costs. (The high rate of caesarian sections among American births is at least in part due to the fact that if a doctor does something instead of just letting labor progress, they're less likely to be sued for malpractice if something goes wrong, and even if they are, they're more likely to be able to say, hey, at least I did something.) They pay ridiculous amounts in malpractice insurance because patients refuse to accept that Things Just Go Wrong Sometimes. (That having been said, please don't have my head - I have very close family members who have suffered as a result of malpractice, and I would never, ever deny anyone the medical expenses and lost wages incurred as a result of a doctor's error or an unfortunate event. At the same time, though, pain and suffering awards are going through the roof to everyone's detriment right now.)

...And that's all off the top of my head right now. These items all relate to and are dependent on one another. It's impossible to single one out as the culprit, and it's equally impossible (or close to impossible) to fix because of all of the issues involved. I don't know what the solution should be. I'm barely just getting my hands around the problem at this point.

"So, what will the FDA enforce?"

I must get asked the question in the title three or four times a week. I don't blame people for wanting to know - clearly, it would make life much easier for just about everyone if we knew and could concentrate on what FDA perceives to be the potential critical points of failure in the industry's work. But I don't know beyond what FDA states in guidance, and I can't read minds, so, due to budget cuts and an attendant lack of a crystal ball, I turn to the next best thing for my answer: FDA Warning Letters.

After reading these letters every day, I've come up with a pat response which, though probably more flippant than it should be, contains a grain of truth:

FDA seems to care most about food products and promotional material. So as long as you don't make something people are going to eat, and you don't claim that your product cures anything, you're pretty much good to go.

Like I said, flippant. But also not without its truth. If you read all of the warning letters sent to companies in recent months, you'll find that the vast majority of them pertain to either food products that were manufactured in environments that were not in compliance with regulations or promotional materials that don't accurately reflect the benefits, risks, and side effects associated with a drug (or device or biologic).

I'm not sure whether I feel that this will change at all as the environment in the industry changes. It feels like now more than ever, the public is demanding "safer" drugs. ("Safer" in quotes because if you're reading this, chances are you know as well as I do that safety is all relative after a certain point.) I'm not sure whether that will translate over time to more stringent regulations (and therefore enforcement) for safety data for new compounds (and what that could potentially mean to the industry), or whether the hue and cry over DTC ads will continue instead. Perhaps both will happen to some extent.