July 21st, 2014


Sovaldi is a novel (for now) treatment for Hepatitis C. Previous treatments for Hep C involved injected interferon and generally did not cure it; interferon is really nasty stuff, also. Over the course of many years - decades even, since during the early part of infection, the person who has Hep C may not even know it - there is increasing damage to the liver, including liver cancer and cirrhosis. Even if a liver is available for transplant (not a given), the process of transplantation is fraught with expense, pain and complications, and likely includes taking immuno-suppressive drugs for the rest of one's life.

The Sovaldi course of treatment is about 12 weeks, with a very high cure rate (90%). Needless to say, everyone who has Hepatitis C (there are actually a few qualifiers here, but not too many -- you have to have one of the right genotypes) would like to take it and Get Better. The company which owns the rights to manufacture, market and sell Sovaldi, Gilead, is charging a lot of money ($84K is a number which comes up frequently) for the course of treatment. However, this is not necessarily more money than the previous treatments (which involved injections and interferon), and may be less -- plus way less awful and way more successful. Further, not having to deal with the chronic costs of hep C is a huge savings: hep C tends to lead to job loss, then caregiver costs, plus cancer treatment and transplant costs. It's pretty horrible. $84K seems extremely cheap compared to that.

Hepatitis C suffers from an association with marginalized groups of people engaging in activities that many people disapprove of (IV drug use, unsterile tattos), altho many people got hepatitis C from blood transfusions before the blood supply was more consistently monitored (or in parts of the world where it is still compromised). It has probably received less attention from researchers than it might have received otherwise.

There is currently a massive debate going on about whether Gilead should/will (be allowed to) charge so much for Sovaldi. From an investor perspective, there are many bears on Gilead, because it is expected that Gilead will be unable to sustain this high price level. Several other, even more effective, treatments for Hepatitis C are expected to come onto the market in the near term, which will result in competition. Many countries other than the United States are much more aggressive about regulating drug pricing. Gilead is not run by a bunch of idiots; they know they'll never sell this thing in markets like Indonesia at this price point and they are already working with generics manufacturers in India to put out a version of the drug for markets in the developing world which costs a few thousand dollars, definitely cheaper than the current standard of care for Hepatitis C there currently.


Here is an example of critical opinion of the pricing of Sovaldi, which includes a description of its development history.


Alas, it is now behind a paywall. It is also an opinion piece, so, grain of salt here. But I intend to use this development history as presented by a critic of Gilead pricing to show how the argumentation is a little disturbing (that is, take the argument against and turn it around as pro).

According to this opinion piece, Raymond Schinazi at Emory University, received a few million dollars in grant money from the US (NIAID) to research HIV and HCV and other things. He developed a drug candidate and then took that candidate and formed Pharmasset. That drug candidate did not go anywhere. Other scientists at Pharmasset worked in related areas came up with other drug candidates. In the course of going through another million dollars (or so) from the US government. It also managed to go through close to a third of a billion dollars from other sources.

"In its early years, it received $1 million in government grants. Its total losses through 2011 came to $314.8 million."

It did, eventually, come up with what would become Sovaldi, and when it became clear it really had something, Gilead bought Pharmasset. For $11 billion dollars.

"Gilead spent tens of millions of dollars to complete Sovaldi's clinical trials. Yet last August, the NIAID issued a news release touting its role in running one of those trials when positive results were reported in JAMA. The government, it turns out, had kept its hand in the development of Sovaldi.

While the risk of failure was always there, the returns on success for stockholders have been nothing short of spectacular. Gilead will recoup its total purchase price in less than three years. If Gilead had paid $5.5 billion, would the drug's price be half as much?

Some argue that the cost of new drugs must cover all the failed R&D efforts within pharmaceutical and biotechnology firms. But if that's true, where's the risk?

It's not fair to ask public and private insurers and patients through their co-pays to be the only parties at risk in the nation's search for miracle breakthroughs. The long history of taxpayer-financed involvement in the development of Sovaldi only adds insult to the financial injury."

Goozner, in essence, argues that the $10 or so million dollars put into this entire process, start to finish, including funding a bunch of drugs that went absolutely nowhere, was unfairly compensated for by the creation of Sovaldi, overwhelmingly funded by private money. It's not completely clear what he wants to happen next, but it sounds like he doesn't really what Gilead to make quite that much money. What sort of return should the US get for its $10 million or so? Plenty of owners of Gilead over the years have lost money, if they ultimately sold it lower than they bought it.

Anyone who invests in ventures like Pharmasset is looking for 10X or 20X. They know that some of these things will fail. All of them might fail. That, Goozner, is where the risk is. After Solvadi is out there and working, and highly desired by everyone suffering from Hepatitis C, it is very easy to think, hey, just regulate the price of that way, way, down, because, after all, paying off that billions of investment in a few years is totes unreasonable.

Well, fine, but what timeframe is Gilead allowed to contemplate for recovering its investment and, for that matter, how much money are they allowed to profit? With competitors coming on the market, if they don't get paid in a few years, they might never recover their purchase price of Pharmasset. True, Pharmasset may produce additional successful treatments -- but if we regulate Sovaldi down to minimal profit, who is going to want to fund more of that? Eventually, we'll be down to the government being the only people interested in participating, and it's clear from this version of the story that the government wasn't actually willing to pony up the hundreds of millions of dollars required to get it done.

It's very easy to argue that once government money is involved, that the other participants in the development process didn't really do any "work". That they were just handed the results of government funded research and allowed to do whatever they wanted with it. The assumption is that startups like Pharmasset don't actually do any real research at all -- all research occurs in a university context and is therefore publicly funded, none of it is funded by private investment looking for big returns in the devoutly desired event called success. And I've heard that argument more than once. But you could make the same argument about integrated circuits. The original ICs were developed with government funding. Everything done since then has been publicly funded by university VLSI research groups, amirite? I mean, there's no way that Intel, or AMD, or, hell, even IBM, they don't do _real_ research there, not like at universities funded by the government. The obvious conclusion is that the feds ought to be able to decide what Apple or Samsung can charge for a smartphone.

That is not somewhere I want to go.

I see the looming fiscal crisis that is the direct, predictable result of very expensive research processes succeeding in finding cures for diseases that were previously incurable. I get it. I don't know how we are going to solve it. Please let's not solve it by destroying the motivation for the beautiful public-private partnerships that resulted in these cures. Because I, for one, want a lot more of them.

Never, Ever, Ever Underestimate the Prevalence of Nutters

Long ago, I used to use "nutter" as a login, a handle, a userid. I used it because I absolutely adored Gaiman and Pratchett's _Good Omens_, and in particular, I adored Agnes. I did also recognize that I was self-labeling as crazy, and I was really good with that part, too.

Because I grew up as a JW, and because my father was sort of top-end working class (electrician), and because my early childhood occurred in the 1970s, my encounters with the "helping professions" and other mental health professionals were profoundly limited. That is, our primary care doctors tried to get us to counselors and our parents said no, because our religion said that that would cause us to lose our faith. So suicide attempts, anorexia, bulimia, depression, and what were, in retrospect, psychotic breaks (not all of this was me, mind you) went entirely unmonitored, untreated (well, I think there may have been vitamin B shots for the anorexia) and poorly managed. Just as it took a while to get the hang of voting and otherwise engaging in good citizenship, it took me a while to get the hang of caring for myself mentally and emotionally, after I quit being a JW. But eventually, I paid attention to my problems, deployed my considerable cognitive resources, and somewhere along the line a boyfriend (possibly more than one, if I'm being honest with myself) asked me if I knew about autism, and when I finally paid attention, I went, hey! There's a particular kind of crazy that is Me! Woot! I had some issues (still do, some days) with whether this is legitimately a disorder in all cases vs. an alternative way of being, and I am a Fervent Believer in the Good Things associated with neurodiversity. But while I continue to believe that age-peer, highly regimented schooling is Not the Best Way to Raise Kids, I also recognize that we live in an imperfect world and that we maybe don't have infinite resources to make everything absolutely the best it can possibly be for everyone all the time, and sticking 20+ kids in a classroom pointed towards an adult at the front to learn stuff in a well-defined and consistently presented way is not an unreasonable compromise.

I like to think this is reality based thinking about how to do things. I sort of disapprove of idealism/True Belief/ideology/faith (cf. raised a JW and am not any more).

Statement of perspective out of the way, I'd like to introduce you to this gentleman:


He has written a book which has generated a lot of seemingly favorable (no zero star, many 4 star) reviews on Amazon.


The lone 2 star review is remarkably restrained: be really careful with this book; it might lead to a delayed dx. But even the 4 star reviews contain statements of this nature:

"I have a kid on the autism spectrum (yeah, I'm pretty sure) and yesterday his brother said "Do you think he's really autistic? Or is he just weird?" It's a fine line, sometimes. If you have a kid with difficulties, this book is really worth reading."

So, basically everyone else's kid is over-diagnosed, even tho the reviewer accepts the legitimacy of the dx for their own kid.

"However, I feel that the author takes the enormity of the mis/over-diagnosis and mis/over-medication crisis a little out of context where he fails to take into account how utterly powerless many parents are to change their child's experience in the classroom -- which for many is over-regimented and abysmally lacking in the normal physical outlets required by healthy, active children - without resorting to seeking out a literal *label* that is the ticket to getting needed accommodations or educational assistance. In other words, teachers are overburdened, budgets are shrinking, all that boring stuff..."

That's really a surprise to me. I was told, right from the very beginning, that the reason to get a dx for my kids was to ensure they received appropriate support from the school system. It has _always_ _always_ _always_ been about integrating with services. It wasn't about drugs. It wasn't about defining pre-emptively what might or might not be possible for them. It was about making sure that they didn't get slotted into some category like "bad kid", when there was something going on with them that wasn't about how hard they were trying, or whether they were from a good home or whatever.

But here's a real doozy (again, from a 4 star review!): "Unfortunately, Gnaulati doesn't work very hard to help distinguish real ADHD/bipolar/autism from false forms: after complaining about fuzzy, over-general definitions from other professionals, he explains the difference mostly in terms of how interacting with different children makes him feel. Likewise, after regretting the tendency to seek medical rather than psychological explanations for child behaviors, he turns to evolutionary psychology and theories of inherent gender difference, as though these aren't based on similarly overblown notions of how much we understand about the workings of the brain. If there's a solution to the problem of over-diagnosis, it's actual scientific rigor, not trading one set of facile assumptions for another."

So despite some extremely serious criticisms of this book, reviewers nevertheless really want to believe what is on offer here. Again, from a 4 star review: "I agree with him, so I have a bias to like the book, I suppose."

This is quackery. I know that a lot of people really, really, really wish that the higher rates of autism diagnoses "proved" that these weren't really autism at all. But I know that my kids are basically just like my sisters and I were when we were little. And our parents when they were little. And aunts and uncles and cousins and grandparents and the more genealogical research I do, the more pervasive this shit looks in my family tree (also, the research that says that ADHD and autism and schizophrenia all tend to show up in relatives of each other? Alas! I have entirely too much anecdata to argue with that thesis.). And while many of us grew up and paid our bills and got jobs and were able to sustain some relationships, we didn't stop being autistic, just because we very carefully avoided ever encountering mental health care, much less getting a diagnosis. We were just miserably bad at social stuff and had weird neurological problems (seizures and migraines -- hell, even the men in my family get migraines. I didn't even know that was _weird_ until a year or so ago) and epic sensory problems. Epic. I spent a lot of time when my kids were young and I was working actively on my reproductive website stuff laughing my head off at people who had a kid with allergies or sensory issues and how difficult it was to find detergents and shampoo and wtf without fragrance. I had to find all that stuff for myself -- and a husband that was the same way so we wouldn't drive each other nuts (well, not nuts in that way, anyway).

So the next time you're wondering what's going to happen when all these little kids diagnosed with autism are All Growed Up, well, remember that there have been untold generations of people with autism before them who didn't receive any accommodations or assistance or supportive therapy. Hopefully, what we are doing will help, at least a little. If, on the other hand, you quail at the idea that the world has that many fucked up, broken, crazy people in it, well, try very hard not to be one of the fucked up, broken, crazy people by descending into denial. Diagnoses are descriptions that offer opportunities to make a better world in the future, through actions we take today. Sometimes that's a prescription for pharmaceuticals. Sometimes that is a suggestion to try therapeutic riding, or a placement in a substantially separate classroom that can be modified in a way to enable a child to learn who isn't able to learn in a mainstream classroom. Sometimes it's a recognition that we'd better pick a career, friends, and romantic partners who are compatible with our particular makeup. (Perhaps someday soon, we'll have data on the efficacy of Disney therapy!)

Is that such a bad thing?

If you think it is, you're just a different kind of nutter. Or, to take a moral perspective, rather than a therapeutic one, a crappy human being.

The last thing I want to point out about Gnaulati is that he exhibits an unusually clear case of how diagnostic communities behave. There were practitioners who would ONLY diagnose autism in conjunction with ID (intellectual disability, you know it by other words that Polite, Well-Educated people don't use any more, altho the abbreviation, MR, is still occasionally deployed). After all, Very Intelligent People must not be Like Those People. There were other practitioners who would ONLY diagnose autism in the absence of ID. You could think of this as more or less like refusing to diagnose pneumonia in someone who had asthma, or requiring pneumonia before diagnosing with asthma. If you squint just right, it sort of looks reasonable, but anyone who has internalized the idea that autism is primarily a disorder of social communication, with a need for routine and some assortment of sensory/neurological stuff going on, is going to realize that autism and substantial intellectual capacity are more than merely compatible -- but often occur separately. That relentless focus on details turns out to be pretty incredible in some contexts, but does not insure measurable intelligence, nor does measured intelligence require a lack of social skills. Gnaulati has outlived his diagnostic community, and is thus forced to take his approach (if you're smart, you must not be autistic! Bad diagnosis!) to the lay public, as he has lost the battle at large so thoroughly that all those efforts to keep Asperger's (with its mandated normal or higher IQ) separate from autism have definitively failed.

When I started thinking about writing this post, I was In a Mood. I stumbled across the Salon excerpt when I was trying to better understand what people meant by the term "introvert" (it's not new to me -- it has just always bugged me and I was trying to articulate why I thought it wasn't a good category to someone and failing), and it just made me angry. I felt like the 2 star reviewer: this is a dangerous book, a dangerous commentator who might well encourage a kind of denial that is bad for the person who needs help, bad for the family trying to help that person, and bad for future society that must somehow manage that person if they do not receive effective assistance in learning to live in the community without hurting themselves and/or others. And I wanted there to be someone to say, hey, this guy is awful. Don't listen to him. What I kept seeing instead were these seemingly favorable comments. But when I drilled down, I started to understand that the favorable comments really didn't take Gnaulati's thesis all that seriously. People really believe in their kids' diagnoses, and they believe that diagnoses are a reasonable real world strategy for connecting kids to the help they need to learn. They just sort of wish that we could all live in a world that let us be our own, nutter selves without having to interact with other people in a structured way. And I guess I can't really argue with that wish, only observe that wishes aren't plans.