Two nonfiction reviews

[rivkat]

Marcia Angell, The Truth About the Drug Companies: How They Deceive Us and What to Do About It: Well, that pretty much sums it up. Drug companies aren’t responsible for most innovative new drugs, most new drugs aren’t innovative, they don’t spend most of their money on research but on marketing new uses and new diseases to us, they make profits that would shame Rockefeller, they own Congress and have an option on the Presidency (as a result of which, a potential FDA head was rejected because of a concern, in the words of Bill Frist, that he was “too concerned about safety”), et cetera. The new prescription drug benefit includes a provision barring the government from negotiating price discounts, a provision both mind-boggling and totally natural under the corrupt circumstances Angell recounts. This is a screed, and a pretty well-backed screed at that. I think Angell condemns “me-too” drugs with too broad a brush, though. Very few drugs approved each year are new molecular entities or otherwise major advances in treatment; often they’re similar to drugs already available for the same condition. This can be wasteful, but sometimes there is an improvement. I’m especially thinking of drugs that can be taken once a day instead of three or more times – the difference between the one-a-day and the 3-a-day is the difference between a drug that people will actually use according to instructions and one that, despite their best intentions, they’ll often neglect to take on time. Angell does make the excellent point that right now most new drugs are only required to show they work better than placebo, but where a treatment exists, it would make a lot of sense to change the standard. She advocates that the standard should require superiority to the existing drug, but parity or superiority in a particular subgroup would probably be worthwhile too, especially since long-term effects can stay unknown for a while. Of course, neither change is likely to happen any time soon, as long as drug companies can afford to buy themselves a nice Congress and a compliant, demoralized FDA.

Bernard Taper, Gomillion versus Lightfoot: Apartheid in Alabama: I got a bunch of books from my dad, who’s cleaning out his study, so expect some strange reviews of books from the 1960s/early 1970s here, including Goffman, Kuhn, and some other classics I’ve never actually read. This is a short book made out of two New Yorker pieces and a bit of followup, about the events surrounding Gomillion v. Lightfoot, the Supreme Court case declaring that Alabama couldn’t gerrymander the boundaries of Tuskegee to exclude basically every black in order to ensure that, even if blacks did manage to register to vote, they wouldn’t be able to participate in governance. What’s striking about this account is how simple, how blunt the tactics of discrimination were. Although they were defended violently and I’d never say they were easy to overcome, it was easy to figure out what was wrong.

Tuskegee had long had “good” race relations, in part because of Booker T. Washington’s insistence that political rights were unnecessary and would be granted in good time if black citizens proved themselves worthy. The gerrymander, designed to turn Tuskegee from a black-majority to a white-majority city in anticipation of the state’s being forced to register more black voters, was pretty decisive proof of the contrary. The Tuskegee Institute had fostered a well-educated, middle-class black citizenry, somewhat disconnected from the poorer rural blacks around them – one brief but compelling moment in Taper’s account comes when he suggests that the black laborers/farmers experienced some gentle schadenfreude when the black professors finally realized that, as far as whites were concerned, they weren’t ever going to be anything but “Negroes,” and that on a good day.

But the most telling moment in the narrative comes from a white businessman who’s just been talking about how good white Tuskegee’s relations with blacks have always been. Taper asks why he’s afraid of blacks voting: “I asked if he didn’t think it possible that his fears were exaggerated – that if Negroes got into office they might treat white citizens with justice. ‘Well, they wouldn’t,’ he said. ‘They couldn’t!’ But how could he be so sure, I asked. He burst out, ‘Listen, if there’s such a thing as hate, there’s gotta be hate in [blacks’] heart for the white man in the South!’” That’s a statement from a man who knows he’s done wrong. These days, with formal segregation gone and the worst excesses of racism routinely decried by top leaders, it’s a lot harder to find a clear enemy.

Comments

[skipthedemon.livejournal.com]

I've grown up here in Birmingham, and the race issue is clearly still not dead. There's a whole lot of what I call "structural segregation". The vast majority of blacks live in the heart of the city with poor schools, a dying downtown, and unreliable public transportation. The middle and upperclasses (and the commerce that follows them) continue to flee further and further south of downtown. They don't care about transportation, because they have big SUVs. They tax themselves to have the best schools in the state, but it only works because each suburb has it's own school system. I'm not sure how to break the cycle, but it makes me very sad.

[boniblithe.livejournal.com]

Angell does make the excellent point that right now most new drugs are only required to show they work better than placebo, but where a treatment exists, it would make a lot of sense to change the standard. She advocates that the standard should require superiority to the existing drug, but parity or superiority in a particular subgroup would probably be worthwhile too, especially since long-term effects can stay unknown for a while.

Just peeking in to say that in Oncology, that is exactly how it is: you must show therapeutic equivalence with a better safety profile, or increased therapeutic benefit over existing treatment. There are no placebo controlled studies in oncology - it's too unethical to not treat terminal disease with at the very least, the best currently approved therapy as a comparator. All of pharma gets painted with the same brush, which is sad. Although when I see our marketing people coming, I can't get away fast enough. *shudder*

That being said, the government needs to wise up and quit nickel-and-diming pharma to death with regulations that bog the process down and tie up everyone in paperwork, dotting i's and crossing t's instead of focusing on design and safety. They also need to quit taking pharma money and quit doing crap like approving Cialis and Viagra to be covered under Medicare.

/rant

[wearemany.livejournal.com]

I'm not a treatment expert, but in my experience in AIDS advocacy, the bigger problem is less about therapy-vs-placebo (because, yes, double-blind studies are generally considered a no-no) and more about therapy from company A-vs-second therapy from company A. pharma companies are starting to do some trials to prove their drug is better than someone else's (though of course this requires that they BUY that competitor's drug for the trial, because they're certainly not getting it for free), but almost never will they admit that their own me-too drug isn't much of an improvement.

however, my biggest gripe continues to be the lack of phase IV (post-marketing) trials, which companies agree to in principle in order to get accelerated approval, and yet almost never execute. this would allow the really important factors mentioned here in comments (side effects, dosing differences) to be made a part of a rigorous trial rather than catch as catch can. it would mean using real-world dosing levels (not the maximums that they can sell w/ safety) and real-world drug competition.

thanks for this review, rivka -- i have yet to actually READ angell's book, just a lot of noise around it. (I also find it interesting you didn't mention her former job, as that seemed to be what got her so much of the press when this came out.)

[boniblithe.livejournal.com]

In fact it was patients in HIV trials who made placebo-controlled trials a thing of the past, because they would enroll in the trial, take their drug to a pharmacy and break the blind and if they were on placebo they'd drop out and go enroll in another trial. Health authorities finally twigged to it and realized that placebo in terminal disease was really a horrible thing, so now they allow head to head comparator studies to carry the same weight that they used to mandate thru placebo control.

We do a lot of phase IV post-marketing trials where I am, but maybe in HIV research it's different. I think the patient population and privacy issues are probably vastly different in HIV vs cancer - people don't get socially ostracized for having cancer and for reporting back about their drug experiences.

I'm hoping to get around to reading Angell's book myself, soon!

[rivkat.livejournal.com]

Great discussion! I think Jerry Avorn's book is better overall, but that's probably an overreaction to Angell's fairly strident tone. It's not as if she doesn't have reasons to be mad.

[londonkds.livejournal.com]

I think Angell condemns “me-too” drugs with too broad a brush, though. Very few drugs approved each year are new molecular entities or otherwise major advances in treatment; often they’re similar to drugs already available for the same condition. This can be wasteful, but sometimes there is an improvement. I’m especially thinking of drugs that can be taken once a day instead of three or more times – the difference between the one-a-day and the 3-a-day is the difference between a drug that people will actually use according to instructions and one that, despite their best intentions, they’ll often neglect to take on time. Angell does make the excellent point that right now most new drugs are only required to show they work better than placebo, but where a treatment exists, it would make a lot of sense to change the standard. She advocates that the standard should require superiority to the existing drug, but parity or superiority in a particular subgroup would probably be worthwhile too, especially since long-term effects can stay unknown for a while.

Angell also fails to have noticed that drugs have side-effects that vary from person to person, so the existence of multiple drugs of similar but slightly different characteristics helps people who might otherwise suffer bad side effects from the One True Drug.

[rivkat.livejournal.com]

Possible, but I'm not aware of how often that happens. From what I've seen, the side effect profile of me-too drugs is often quite similar to that of the benchmark drug. But you're right that a difference in safety ought to matter.

[londonkds.livejournal.com]

Even if the general side-effect profile is the same, individual patients may find that they don't get the side effects from one drug that they do from a very similar one. Even the actual effectiveness of two similar drugs can be completely different for two different people due to personal idiosyncracies. I've personally been put on a drug for hay fever which was the official "ideal" one and found that it simply didn't work. The one which works best for me is usually a second-line drug because it causes unpleasant side effects in some people, but I have no problems tolerating it at all. Just ask one of the many depressed people on LJ about how different the effects of two allegedly all-but-identical antidepressants can be.

The important thing is that the published assessment of a drug relates to the mythical "average" person and an individual will always react to it in a slightly different way. Drug companies and doctors don't like to admit it because it shows how far we still are from being able to make perfect predictions in medicine. But if they'd admit it, they'd be able to explain why, yes, we do need several different drugs for the same condition if everybody is going to be able to get one that effectively treats their condition with minimal side effects. (The anti-drug industry person would probably reply that the drug company's job is to produce a drug that cures everyone with no side effects but there is zero chance of that until we know far, far more about how the human body than we do now. And probably, even then, there will be no drug that is ideal for every single person because of human variability.)

[the_rck]

It's actually fairly common. Over the course of my lifetime, I've taken a lot of different medications for different conditions, and it's always a juggling act. Not only do my doctor and I have to look at how effective a particular med is for me personally, but we also have to look at whether or not it has a potential interaction with the other things I'm taking. Then we consider side effects. Very often, we've tried several different medications before settling on one that works.

An example-- The first choice asthma inhaler for the sort of asthma I have, makes my heart race and makes me otherwise edgy and uncomfortable, so I use a different medication. This is the opposite reaction from what most people experience (which is why the first med is preferred).

Another example-- I take zantac for acid reflux. When the problem first came up, about 10 years ago, we tried all the medications then available. The first we tried made the problem much worse. The second worked but I had a hard time finding a pharmacy that carried it. Years later, while pregnant, I switched to zantac which the gastroenterologist said sometimes is more effective during pregnancy than the other medication. I found no benefit in symptoms, but all the pharmacies carried the stuff, so I've stayed with it. It's no longer as effective as it was, so we're looking at other drugs in the same class to try.

[rivkat.livejournal.com]

That's really interesting to know. I wonder whether it would be possible, for example, to test new drugs in people for whom the current drugs don't work well. That might be a better way to get at the issue of redundant versus useful drugs.

[the_rck]

Well, the current preference is to study drugs in healthy adult males with no other medications or complicating health issues because it makes it easier to be sure that the drug is responsible if something happens (and because nobody's willing to accept the liability if the drug turns out to cause permanent reproductive problems for a woman or birth defects if she gets pregnant while on it). Basically, they're trying to control as many factors as possible. This means that many side effects, drug interactions, etc. only show up once the medication's in broader use. (It also means that doses are calibrated for average male weights and that some medications considered very effective generally aren't because they don't help women as much as they do men.)

This is the sort of stuff that people advocating genetic profiling for medical purposes are aiming at, long term-- A lot of people believe that genetics (which dictates individual biochemistry to some extent) will reveal which medications will or won't work and which will provoke allergic reactions. But the positives of genetic profiling can't obscure the potential negatives in terms of employment and insurance discrimination. The whole issue is *very* messy.

Another factor to consider is that drug companies are looking for profits. Many won't bother trying to develop medications unless there's a large enough potential market. Cholesterol's common and profitable, so's ADHD and cancer and... But obscure diseases that affect fewer than a thousand people in the U.S. don't repay investment and can't. (There was a recent article in Discover magazine that mentioned this with regard to a particular genetic disorder that causes rapid, premature aging. It wasn't last month's issue or, I think, the one before.) I suspect that this may be a bigger cause of copycat drugs than anything else.