Before you get pissy about Viagra you should realize that it was developed as a blood pressure medication. I'm quite well aware of that. And there is some evidence more recently that it may be quite helpful with a deadly pulmonary vascular disease as well (PPH). And you may not be aware that minoxidil (Rogaine) was originally an antihypertensive as well and finasteride (Proscar and Propecia) was originally a drug for prostate enlargement. However, that doesn't explain all the money spent on developing Levitra and Cialis, now does it? Nor does it explain why Merck who sold Proscar 5mg then sold the 1mg Propecia tablet for the same price recast the pill for Proscar so that it would be harder to divide in quarters. They did this so that they could prevent people from quartering the less expensive 5mg tablet rather than pay the same price for a 1mg tablet.
Of course, the drug manufacturer should be compensated for their manufacturing costs, but they shouldn't have the right to set an arbitrary price on the drug for hundreds of percent of profit. Especially when they didn't make the initial investment in developing the drug. Its really scary but they do exactly that with pricing, here is a quite scary NYT article on their pricing of cancer drugs based on 'what the market will bear'
From the times: http://www.nytimes.com/2006/02/15/business/15drug.html
Until now, drug makers have typically defended high prices by noting the cost of developing new medicines. But executives at Genentech and its majority owner, Roche, are now using a separate argument -- citing the inherent value of life-sustaining therapies.
If society wants the benefits, they say, it must be ready to spend more for treatments like Avastin and another of the company's cancer drugs, Herceptin, which sells for $40,000 a year. Its obscene really. Its Pharma saying well, how much is your life really worth to you?
Now, explain for me, just briefly, why the universities don't do that last step themselves? I mean, if it's so easy and would generate for them superprofits...? Because generally academics != good businessman?
For the same reason that I spent an entire day in clinic today (and do so twice a week for the past three years) working for exactly $0 while I generally get about $1500/day at my other job? Because I think its important and it's the right thing to do and that's more important to me than making money?
Because not everyone is a Machiavellian tool and some of us still remember why we entered the health care field?
Though I did not say that it was easy. It's also not free and you have an infrastructure to do it. I think Pharma certainly should be paid a fair amount for their work. However since they are the single industry with the greatest profits (compared with all other industries) and because they spend more on direct to consumer advertising and giving physicians plastic pancreases and free pizza than they do on research, I don't believe what they are getting is fair recompense for their work.
The biggest issue I have with government control is that it tends to be overreaching. If a bunch of pharma companies all have clinical trials going a doctor can choose to participate or not in any trials he thinks will benefit his patients the most. I'm sure that if government were running the show the doctor MIGHT get a chance to opt out, but if he participated they would dictate what drugs he'd be testing. After all, we can't have doctors opting to test wart removers when the acne lobby is so strong. One might hope that this would lead to the most important drugs being prioritized, but "most important" usually translates to "most politically important" when the government is involved. These are two different issues. It is certainly the case that diseases with more political clout get a disproportionate amount of funding, but that is hardly all due to NIH's decisions about what gets funded. For example there is a disproportionately greater amount of research money spent on Type 1 diabetes (which effects far fewer people) than there is on Type 2 diabetes. But that is not because of the NIH's grant process. The NIH fairly apportions funds according to the need, but the JDRF pumps a ton of money into research on Type 1 diabetes. So it's the private interests (who in this case are thinking of the children) rather than the public funding that makes the funding disproportionate to need.
That doesn't mean that I think the government is immune from these kind of influences. Hell breast cancer attached to anything gets a lot of funding, and if you want to kill a research proposal just use the phrase 'non-punitive drug treatment' or elective abortion. However, while both the government and the market are influenced by forces making them imperfect stewards of the research dollars, I think the problems using market forces are far greater than those we see in the current NIH funding scheme.
I am a medicine geek and will offer a simple translation for computer geeks who may be less familiar with this situation. Put very simply:
Big Pharma = Micro$oft, SCO, MPAA/RIAA
MSF, Developing nations like Brazil and India who produce medicines for the developing world in violation of the patent = Linux, EFF, University of Oregon et al.
They are recovering more of the cost of marketing (which takes a greater share of their budget than basic research), but don't buy the myth of the $800 million dollar drug.
From Physicians for a National Health Program: http://www.pnhp.org/news/2004/february/will_lower_drug_pric.php
16. The average amount of research funds the drug industry needs to recover appears to be much less than the industry's figure of $800 million per new drug approved (NDA).
The $800 million figure is based on the small unrepresentative subsample of all new drugs. It excludes the majority of "new" drugs that are extensions or new administrations of existing drugs, as well as all drugs developed by NIH, universities, foundations, foreign teams, or others that have been licensed in or bought. Variations on existing drugs probably cost much less because so much of the work has already been done and trials are simpler.
About half of the $800 million figure consists of "opportunity costs", the money that would have been made if the R&D funds had been invested in equities, in effect a presumed profit built in and compounded every year and then called a "cost." Drug companies then expect to make a profit on this compounded profit, as well as on their actual costs. Minus the built-in profits, R&D costs would average about $108 million 93% of the time and $400 million 7% of the time.
The $800 million estimate also does not include taxpayers' subsidies via deductions and credits and untaxed profits (DiMasi, Hansen, and Grabowski 2003; DiMasi, Hansen, Grabowski et al. 1991). Net R&D costs are then still lower.
Contrary to some press reports from the industry, screening for new compounds is becoming faster and more efficient and the time from initial testing to approval has shortened substantially (Kaitin and Healy 2000). The large size of trials seems more due to signing up specialists to lock in substantial market share. Advertising firms are now running clinical trials (Bassand, Martin, Ryden et al. 2002; Peterson 2002; Moyers 2002).
Your taxes already do pay for research - through NIH grants, tax breaks for pharmaceutical companies, and then after the drug is almost fully developed the government often gives the patent to an industry 'partner' to bring to market. A good example is AZT, the first ever anti-HIV medicine. The lion's share of the cost for developing AZT was paid by our tax dollars. Then Glaxo-Wellcome stepped in for the last bit and viola, they have an exclusive right to sell a life saving drug for whatever the market will bear.
From Physicians for a National Health Program's website: "15. Taxpayers pay for most research costs, and many clinical trials as well. In 2000, for example, industry spent 18% of its $13 billion for R&D on basic research, or $2.3 billion in gross costs (National Science Foundation 2003). All of that money was subsidized by taxpayers through deductions and tax credits. Taxpayers also paid for all $18 billion in NIH funds, as well as for R&D funds in the Department of Defense and other public budgets. Most of that money went for basic research to discover breakthrough drugs, and public money also supports more than 5000 clinical trials (Bassand, Martin, Ryden et al. 2002). Taxpayer contributions are similar in more recent years, only larger." http://www.pnhp.org/news/2004/february/will_lower_drug_pric.php
So they paid 2.3 billion (tax subsidized), and we kicked in 18 billion. Then they get to charge us for access to the drugs for which we paid 95% of the basic research costs.
Of course that is the reason that while you may not trust the government, they could be a much better steward of medical research than market forces. Market based R&D is inherently morally corrupt. It can't be otherwise. If its not obvious because of the fact that more R&D is spent developing drugs to give octogenarians a hard-on and a full head of hair than to offer effective treatment for malaria that kills millions each year in the developing world, MSF gives a great summary of the reasons that market based R&D is wrong: http://www.accessmed-msf.org/main/medical-innovation/introduction-to-medical-innovation/what-is-wrong-with-r-d-today/
Though I do agree with you that at present I don't trust the government. Not that they do bad research... the NIH and the researchers they fund are amazing. But I don't trust the corrupt system that gives the breakthrough drugs that the government develops into the hands of private industry so that they can extort millions of Americans for the price that the 'market will bear' for drugs they may need to survive.
I would agree that CT is overutilized as an imaging modality. However, CT is a unique situation that makes it a poor choice for displaying the tendency of modern American MDs to overdiagnose or overtreat. For CT, the problem is that there is apparently a widespread misunderstanding of the risk of the procedure. I think there is a pretty reasonable understanding of the risks of CT scan among physicians. I can't think of any physician who would say that a CT is comparable to a plain radiograph as you suggested. And I rattled off that 1/500 figure without looking it up. But while you can know the answer to the question "what would I suggest if it were my kid/spouse/mother?" that isn't always what you recommend because of defensive medicine.
For most other situations, I would bet that the risk/benefit ratio is not the problem: it's more likely to be either patient demands that the doctor _do_ something, fear of malpractice suits (as you mentioned), or it could even be an attempt to "get their money's worth." That last point is definitely more prominent if you look at MRI as a modality: the units are extremely expensive and yet have minimal risk if used properly. My feeling is that, if MRI is overprescribed, it is probably for reasons of cost-recovery--which is also very sad. I don't think its so much the 'money's worth' idea, but that people have pretty unrealistic expectations of medicine. (It ain't like on ER.) They expect that if you come to the ER with abdominal pain, you will get a definitive answer as to what is going on and be offered treatment that will definitively fix the problem. However in reality, 2/3 of the time with a good history and physical I can be comfortable that its quite unlikely to be something dangerous but is more likely gas, ovulation, a poo cramp, or evil humors. But people are less likely to buy that idea that if they have no red-flags for a bad diagnosis, its ok to assume it is something benign, go home, and return if it changes. Without 'a test' they don't feel like that kind of distinction can be made. So we often do the expected dog and pony show. However I think its less wanting something that they think costs a lot, but rather they want something that they think gives an objective and 'real' answer (which often times lab tests and CT don't do anyway).
Is it normal to transplant livers across blood types? You can accept an Rh mismatch for a liver transplantation. And if you are going to die tomorrow, death from rejection in 5 years is a better deal.
This sounds like a nearly missed case of malpractice. No. First of all this was not in the US. It is a uniquely American thing to assume that unless 1) All care is 100% perfect and 2) The outcome is 100% perfect, that you should sue your physician for malpractice.
Despite the best care, sometimes bad things happen and people die. And sometimes the best care isn't possible, and you do the best you can as the doctors did in this case. The ideal is a perfect blood type and HLA match, however failing to act because you don't have a perfect match would have resulted in this child's death. Perfect in this case is the enemy of good.
Unfortunately this sort of attitude creates no end to trouble and causes both inappropriately aggressive therapeutics and diagnostics in the US as opposed to elsewhere. There is a saying amongst OB/Gyns - you don't get sued for the C-Section that you do, you get sued for the C-Section you don't do. So surprise.... the US has a higher section rate for women. Similarly, in the US your child with belly pain is much more likely to get a CT scan to rule out appendicitis. Doing the CT doesn't get you sued, but failing to do it eventually will (because there is always going to be that very small number of kids with an appy that presented very atypically.) However, if you do 500 Abdominal CTs in kids less than 15, you will ultimately cause one excess cancer death in that group. But you won't get sued when the kid dies of renal cell cancer in his 40's. So kids with a very low risk of appendicitis instead of being observed (maybe even at home with responsible parents) will more often in the US get a trip to the donut and the resulting dose of radiation to their more vulnerable bodies.
While it might seem that holding physicians to unreasonable expectations is beneficial, in the long run you will get worse care due to the practice of defensive medicine.
Yes, but momma is certain to know whether she got assisted reproductive technology (and hence this risk) while daddy's doesn't always know if the wrong sperm were implanted into momma.
If her immune system has been replaced by her donors, won't her other organs/tissues (her own) be rejected by her new (her donor's) immune system? Yes, but GVHD is not as bad as the combination of host versus transplant graft plus immune suppression. There is some talk of doing BMTs with other solid organ transplants to do exactly what this girl did spontaneously. Also, in the case of GVHD, the immune system is attacking OEM parts so they are healthier to start with than transplanted tissue.
They gave her a liver from someone with a different blood type?!? I know other markers as well as blood type are taken into account (and in hepatic Tx urgency is another factor), but I thought a blood type match was the minimum requirement Not if you are going to die tomorrow. Once we get the liver equivalent of dialysis, this will change, but until then the threat of death from fulminant liver failure trumps the concern over graft rejection. Plus in kids there is a little more wiggle room (since they have more adaptable immune systems.) So while the ABO type has to be the same (which they were in this case), they will accept Rh type mismatches. Though they were actually a really poor match. The HLA status of the donor was A34,68;B50,76;DR4,13, while the recipient's HLA status was A2,24;B37,62;DR7,9. That is, 0 for 6.
Nope. Its the boy's immune system now. From the NEJM article:
"The change in this patient from group O, RhD-negative blood to group O, RhD-positive blood suggested the development of chimerism by engraftment of the recipient marrow from passenger hematopoietic stem cells within the transplanted liver. Fluorescence in situ hybridization studies for the X and Y chromosomes were performed on a bone marrow aspirate and peripheral-blood lymphocytes 3 months after the onset of hemolysis (post-transplantation day 395).2 Analysis of cells from the marrow, sorted by means of flow cytometry, showed that they were male (XY) in myeloid, erythroid, and CD19+ B cells. Analysis of peripheral-blood aliquots revealed a predominantly male (donor) population: of 50 T cells, 94% were male and 6% were female; of 50 B cells, 98% were male and 2% were female; of 50 granulocytes, 100% were male; and of 50 natural killer cells, 100% were male" And that was while she was still on an immune suppression regimen. After they found the results above, they made a decision: "These results suggested that the hemolysis was due to the production of antibodies by residual B lymphocytes in the recipient against engrafted erythroid cells from the donor. A choice between two therapeutic options was then considered: the use of rituximab, an anti-CD20 monoclonal antibody, which would deplete all B cells (both host and donor cells), or withdrawal of all immunosuppressive therapy to allow full engraftment. The decision was made to withdraw the immunosuppressive therapy." After which her immune system essentially became entirely that of the boy whose liver she received. Even to the point that since he hadn't gotten his MMR vaccine, she lost her immunity to measles, mumps, and rubella (which she regained when she was re-immunized.)
Except that both of her parents are also Rh negative. From the NEJM article: "Nine months after transplantation, a small-bowel obstruction developed, requiring surgical division of adhesions and resection of an ileal band. Routine preoperative blood grouping revealed that the patient's blood group had changed from O, RhD-negative, to O, RhD-positive (the donor's blood group), and a weakly positive direct antiglobulin test indicated coating of red blood cells with IgG antibodies. At that time, there was no evidence of spherocytosis on the blood film to suggest hemolysis; the hemoglobin level was 95 g per liter. This finding was confirmed by the Australian Red Cross Blood Service. Both parents had group O, RhD-negative blood with the phenotype ccdee, whereas their daughter's phenotype was now cDEe. However, serum samples showed mixed-field reactions with anti-D and anti-E typing."
Of course the parents genotype is no absolute guarantee, as it is always "momma's baby, daddy's maybe" but it sounds like they have this pretty well nailed down. She really did develop chimerism.
Yes, its called Graft Versus Host Disease (GVDH), and is a common complication of bone marrow transplantation. If it happens, it manifests as skin, liver, and gut problems mostly. Liver obviously isn't going to be a problem for her, and it sounds like from the original NEJM article I just read that she hasn't had any other manifestations of GVHD. If you are going to get bad GVHD its usually early on, so she's out of that woods, but there is always chronic GVHD manifestations that will show with time.
Though given a choice, I'd take the GVHD risk, lose the immunosuppressants, and never worry that my liver graft would fail. All in all she's a hella lucky kid.
They really ought to teach basic probability theory in schools... Or maybe basic biology maybe? The Hardy-Weinberg equation plus a little basic algebra solves the problem:
p + q = 1
p^2 + 2pq + q^2 = 1
P and q are the frequency of a specific gene (assuming there are only two variants, but lets KISS.) Each organism has two copies of a given gene. They can be pp, pq, or qq. So the number of p genes and q genes must equal 100%. And the number of people who are pp, qp, or qq must equal 100%, hence the two equations.
In the case of a simple autosomal recessive gene, the disease exists when an individual is qq. So qq = 1/2000 = 0.0005. So q (the prevalence of the allele) is 0.02. So you would expect that 1/50 people has the q gene (almost all of them as heterozygotes who have one p and one q gene.) If a gene exists in 1/50 people and you sample 1000, the odds that you wouldn't find it is pretty remote.
Do you allow no distinction between ceremonial rules, and rules involving inherent moral/ethical concerns? Oh, you mean like slavery? Lev. 25:44 says its quite hunky-dory as long as they are from neighboring states. Like say for those of us in the USA... Canada.
Do you think that ancient Hebrews viewed dietary laws (prohibition of shrimp) and the command about mixed fabric as moral issues, in the same sense as murder, adultery, theft, and injustice? Quite likely they viewed them differently. But then I also think the issue of the morality of slavery is in the category of injustice rather than fashion and food sense.
If so, why? If not, why base your arguments on absurd equivocation? Its only absurd equivocation if you are unfamiliar with the OT. I'm not, but apparently you are. Why not go have a read and they we can talk a bit more, k?
Of course you could make that claim of absurd equivocation if you accepted as a premise that slavery was not necessarily immoral, but rather simply unfashionable? Though I am guessing you don't want to go there, huh?
When religion doesn't get it right, people abandon it completely. No they don't. They just reinterpret the primary tenets of the religion to suit their current desired conclusions. Religious works and religious beliefs are interpreted in the light of the present society and its prejudices. Rather than being taken at face value, they are used to justify what people want to believe. For example, there is no real prohibition against abortion in the Christian Bible. For another example, the selective interpretation of Leviticus as condemnation of homosexuality while ignoring the condemnation of poly-cotton blends and Red Lobster.
The reason is that in its original form, it was a noun that didn't have a plural form. It meant a substance that was toxic or dangerous in a general sense. So its like saying radiation is toxic. You wouldn't speak about 'radiations' but talk about radiation being toxic. So while 'radiations' is technically correct we as speakers of English don't use that plural.
The ancient speakers of Latin similarly didn't use a plural form of virus, so when people pluralize it using the rules of ancient Latin they come off like Bush speaking of the internets: they don't know WTF they are talking about but would like to sound as though they do. Sigh. At least its better than when he talks about nucular power.
But, call me cynical, this would leave no recurring income for vaccine makers. Um, cynical wasn't exactly the word I was thinking of. Though since you can't seem to afford a clue, I'll give you one. Vaccine research is a money-loser unless you come up with an effective vaccine for western diseases - and even then its risky. At best vaccines generate $6 billion annually - that's about 1.5% of the annual pharmaceutical market worldwide. The problem is, an effective vaccine is used only a few times, and is highly cost effective. So there is not so much profit to be made. Moreover, you will get exactly zero profit with a vaccine that treats non-western diseases. People who would benefit from the Ebola vaccine couldn't pay enough to generate profits.
Before all the bat-lovers start crying foul I would like to point out that it is only ebola's high mortality rate that keeps it contained. IANABL, but the problem with that is that high mortality is only a small part of what keeps it contained. It is also kept contained because of a short incubation period (HIV escaped because you can have it an be infectious years before you get sick), method of transmission (body fluids largely), etc.
Although on one hand i support them, ebola is tooo dangerous to escape from the funny farm. if it had been smallpox or something it would be understandable. Smallpox is far more dangerous and has killed more than a thousand times as many people as Ebola. Ebola is actually relatively easy to contain, though quite deadly. Smallpox is deadly and far more easily spread. And most people under 40 in the developed world are not vaccinated against smallpox. So a smallpox release has a far greater potential danger.
How much do we know about virii to safely declare legally that this ebola virus would not leap from monkeys to humans. First, the standard English plural of virus is viruses. Second, I don't think the courts have anything to do with whether or not a crippled virus is safe any more than the Kansas school board determines whether Creationism is science.
As much as I'd like to find a treatment/vaccine for something as nasty as Ebola, I'm not so sure tinkering around with its genetic code like this is such a good idea. Well, then pretty much most of biomedical research on infectious agents is shit outta luck. How do you think he get live attenuated vaccines? How do you think a lot of HIV research is done?
Like others, I can't help but think about the paraphrased quote from Jurassic Park, "Life will find a way"; if that ever happens and that modified Ebola mutates and gets out of isolation, we are in a world of shit. Like others I can't help but hope that research decision-makers and funders don't get their ideas about what research should be undertaken from bad science fiction.
(Note I said 'bad science fiction'. That does not imply that the fed shouldn't fund research into making a holodeck. That would be cool.)
Nothing is truly safe... It is all a question of odds. The real question is which you'd rather do, swallow a beaker of this crippled Ebola or have a seatmate on a plane flight with EDRTB? Swallow a beaker of crippled Ebola or be on the Bay Bridge in a 6.0 earthquake centered in the bay area? Swallow a beaker of Ebola or go a month without wearing a seatbelt? If TFA accurately portrays the research done, I'd pick the former each time.
They developed a monkey kidney cell line so that they produced a protein that is foreign to primates, and otherwise wouldn't ever be found in a monkey or human cell. So unless you've been genetically engineered to make an Ebola virus protein in your kidneys, I think you'll be safe.
I am not claiming to be some fancy emergency room doctor or whatnot. I am just saying what I have been trained to do. If it will save the life of one of my friends, I am going to do it. Say whatever insults you want to me. I know what I have been trained to do, and I am going to do it exactly as I have been trained. Oooh, I am a 'fancy emergency room doctor'? My aren't you being quaint in a poorly executed attempt at an Argumentum ad Verecundiam (tradition.) That is, you are attempting to negate the readily verifiable evidence that tourniquets are essentially not used as an emergency treatment for hemorrhage in the the developed world today within emergency medicine, EMS, or as part of ATLS (Advanced Trauma Life Support - promulgated by the American College of Surgeons.) You would also like to disregard all the evidence that is readily available about the dangers of tourniquets within the medical literature. (Just search Medline with the terms tourniquet and ischemia.) So you make an appeal to the authority of tradition: that's how you were taught to do, so you will do it in an unthinking fashion regardless of the dangers that it poses.
Unlike your nice, clean emergency room, we don't have all the fancy tools that you do. We have only what we carry, and all that we carry adds weight. We can't afford to have the latest and greatest in medical care that you obviously have access to. We have a small pack of basic medical supplies, dressings, a couple IV kits, and the tourniquet. That's it. Sorry if it isn't good enough for you, but for us, it saves lives. Perhaps you didn't notice, but I also said I'd never used a tourniquet in all the years that I did EMS either. And ATLS, which is designed for both pre-hospital and hospital based trauma resuscitation actively discourages their use. But just as a reminder: you and I and pretty much everyone reading this conversation are not in a jungle. I suspect that you are sitting your fat ass in front of your computer, eating a bag of cheetos, and smoking a cigarette. And since we aren't in a jungle, if someone is hurt, how about you just call 911, let the professionals take care of it and try not to hurt yourself or anyone else with your painfully out of date information?
I don't know what the hell your problem is, but I am done with this conversation. Excellent! Though its no problem. In fact, you are quite entertaining.
Slashdot Mirror
From the times: http://www.nytimes.com/2006/02/15/business/15drug.html Until now, drug makers have typically defended high prices by noting the cost of developing new medicines. But executives at Genentech and its majority owner, Roche, are now using a separate argument -- citing the inherent value of life-sustaining therapies.
If society wants the benefits, they say, it must be ready to spend more for treatments like Avastin and another of the company's cancer drugs, Herceptin, which sells for $40,000 a year. Its obscene really. Its Pharma saying well, how much is your life really worth to you?
For the same reason that I spent an entire day in clinic today (and do so twice a week for the past three years) working for exactly $0 while I generally get about $1500/day at my other job? Because I think its important and it's the right thing to do and that's more important to me than making money?
Because not everyone is a Machiavellian tool and some of us still remember why we entered the health care field?
Though I did not say that it was easy. It's also not free and you have an infrastructure to do it. I think Pharma certainly should be paid a fair amount for their work. However since they are the single industry with the greatest profits (compared with all other industries) and because they spend more on direct to consumer advertising and giving physicians plastic pancreases and free pizza than they do on research, I don't believe what they are getting is fair recompense for their work.
That doesn't mean that I think the government is immune from these kind of influences. Hell breast cancer attached to anything gets a lot of funding, and if you want to kill a research proposal just use the phrase 'non-punitive drug treatment' or elective abortion. However, while both the government and the market are influenced by forces making them imperfect stewards of the research dollars, I think the problems using market forces are far greater than those we see in the current NIH funding scheme.
I am a medicine geek and will offer a simple translation for computer geeks who may be less familiar with this situation. Put very simply:
Big Pharma = Micro$oft, SCO, MPAA/RIAA
MSF, Developing nations like Brazil and India who produce medicines for the developing world in violation of the patent = Linux, EFF, University of Oregon et al.
The $800 million figure is based on the small unrepresentative subsample of all new drugs. It excludes the majority of "new" drugs that are extensions or new administrations of existing drugs, as well as all drugs developed by NIH, universities, foundations, foreign teams, or others that have been licensed in or bought. Variations on existing drugs probably cost much less because so much of the work has already been done and trials are simpler.
About half of the $800 million figure consists of "opportunity costs", the money that would have been made if the R&D funds had been invested in equities, in effect a presumed profit built in and compounded every year and then called a "cost." Drug companies then expect to make a profit on this compounded profit, as well as on their actual costs. Minus the built-in profits, R&D costs would average about $108 million 93% of the time and $400 million 7% of the time.
The $800 million estimate also does not include taxpayers' subsidies via deductions and credits and untaxed profits (DiMasi, Hansen, and Grabowski 2003; DiMasi, Hansen, Grabowski et al. 1991). Net R&D costs are then still lower.
Contrary to some press reports from the industry, screening for new compounds is becoming faster and more efficient and the time from initial testing to approval has shortened substantially (Kaitin and Healy 2000). The large size of trials seems more due to signing up specialists to lock in substantial market share. Advertising firms are now running clinical trials (Bassand, Martin, Ryden et al. 2002; Peterson 2002; Moyers 2002).
Your taxes already do pay for research - through NIH grants, tax breaks for pharmaceutical companies, and then after the drug is almost fully developed the government often gives the patent to an industry 'partner' to bring to market. A good example is AZT, the first ever anti-HIV medicine. The lion's share of the cost for developing AZT was paid by our tax dollars. Then Glaxo-Wellcome stepped in for the last bit and viola, they have an exclusive right to sell a life saving drug for whatever the market will bear.
From Physicians for a National Health Program's website: "15. Taxpayers pay for most research costs, and many clinical trials as well. In 2000, for example, industry spent 18% of its $13 billion for R&D on basic research, or $2.3 billion in gross costs (National Science Foundation 2003). All of that money was subsidized by taxpayers through deductions and tax credits. Taxpayers also paid for all $18 billion in NIH funds, as well as for R&D funds in the Department of Defense and other public budgets. Most of that money went for basic research to discover breakthrough drugs, and public money also supports more than 5000 clinical trials (Bassand, Martin, Ryden et al. 2002). Taxpayer contributions are similar in more recent years, only larger." http://www.pnhp.org/news/2004/february/will_lower_drug_pric.php
So they paid 2.3 billion (tax subsidized), and we kicked in 18 billion. Then they get to charge us for access to the drugs for which we paid 95% of the basic research costs.
Though you may say that PNHP is a bunch of hippies, so if you prefer a more grandfatherly source the AARP do a decent job too: http://www.aarp.org/bulletin/prescription/double_taxation.html
Of course that is the reason that while you may not trust the government, they could be a much better steward of medical research than market forces. Market based R&D is inherently morally corrupt. It can't be otherwise. If its not obvious because of the fact that more R&D is spent developing drugs to give octogenarians a hard-on and a full head of hair than to offer effective treatment for malaria that kills millions each year in the developing world, MSF gives a great summary of the reasons that market based R&D is wrong: http://www.accessmed-msf.org/main/medical-innovation/introduction-to-medical-innovation/what-is-wrong-with-r-d-today/
Though I do agree with you that at present I don't trust the government. Not that they do bad research... the NIH and the researchers they fund are amazing. But I don't trust the corrupt system that gives the breakthrough drugs that the government develops into the hands of private industry so that they can extort millions of Americans for the price that the 'market will bear' for drugs they may need to survive.
Despite the best care, sometimes bad things happen and people die. And sometimes the best care isn't possible, and you do the best you can as the doctors did in this case. The ideal is a perfect blood type and HLA match, however failing to act because you don't have a perfect match would have resulted in this child's death. Perfect in this case is the enemy of good.
Unfortunately this sort of attitude creates no end to trouble and causes both inappropriately aggressive therapeutics and diagnostics in the US as opposed to elsewhere. There is a saying amongst OB/Gyns - you don't get sued for the C-Section that you do, you get sued for the C-Section you don't do. So surprise.... the US has a higher section rate for women. Similarly, in the US your child with belly pain is much more likely to get a CT scan to rule out appendicitis. Doing the CT doesn't get you sued, but failing to do it eventually will (because there is always going to be that very small number of kids with an appy that presented very atypically.) However, if you do 500 Abdominal CTs in kids less than 15, you will ultimately cause one excess cancer death in that group. But you won't get sued when the kid dies of renal cell cancer in his 40's. So kids with a very low risk of appendicitis instead of being observed (maybe even at home with responsible parents) will more often in the US get a trip to the donut and the resulting dose of radiation to their more vulnerable bodies.
While it might seem that holding physicians to unreasonable expectations is beneficial, in the long run you will get worse care due to the practice of defensive medicine.
Yes, but momma is certain to know whether she got assisted reproductive technology (and hence this risk) while daddy's doesn't always know if the wrong sperm were implanted into momma.
Except that both of her parents are also Rh negative. From the NEJM article: "Nine months after transplantation, a small-bowel obstruction developed, requiring surgical division of adhesions and resection of an ileal band. Routine preoperative blood grouping revealed that the patient's blood group had changed from O, RhD-negative, to O, RhD-positive (the donor's blood group), and a weakly positive direct antiglobulin test indicated coating of red blood cells with IgG antibodies. At that time, there was no evidence of spherocytosis on the blood film to suggest hemolysis; the hemoglobin level was 95 g per liter. This finding was confirmed by the Australian Red Cross Blood Service. Both parents had group O, RhD-negative blood with the phenotype ccdee, whereas their daughter's phenotype was now cDEe. However, serum samples showed mixed-field reactions with anti-D and anti-E typing."
Of course the parents genotype is no absolute guarantee, as it is always "momma's baby, daddy's maybe" but it sounds like they have this pretty well nailed down. She really did develop chimerism.
Yes, its called Graft Versus Host Disease (GVDH), and is a common complication of bone marrow transplantation. If it happens, it manifests as skin, liver, and gut problems mostly. Liver obviously isn't going to be a problem for her, and it sounds like from the original NEJM article I just read that she hasn't had any other manifestations of GVHD. If you are going to get bad GVHD its usually early on, so she's out of that woods, but there is always chronic GVHD manifestations that will show with time.
Though given a choice, I'd take the GVHD risk, lose the immunosuppressants, and never worry that my liver graft would fail. All in all she's a hella lucky kid.
p + q = 1
p^2 + 2pq + q^2 = 1
P and q are the frequency of a specific gene (assuming there are only two variants, but lets KISS.) Each organism has two copies of a given gene. They can be pp, pq, or qq. So the number of p genes and q genes must equal 100%. And the number of people who are pp, qp, or qq must equal 100%, hence the two equations.
In the case of a simple autosomal recessive gene, the disease exists when an individual is qq. So qq = 1/2000 = 0.0005. So q (the prevalence of the allele) is 0.02. So you would expect that 1/50 people has the q gene (almost all of them as heterozygotes who have one p and one q gene.) If a gene exists in 1/50 people and you sample 1000, the odds that you wouldn't find it is pretty remote.
There fixed it for you. No need to thank me.
Of course you could make that claim of absurd equivocation if you accepted as a premise that slavery was not necessarily immoral, but rather simply unfashionable? Though I am guessing you don't want to go there, huh?
Well, unless you are someone who strictly interprets the OT: http://www.godhatesshrimp.com/
The reason is that in its original form, it was a noun that didn't have a plural form. It meant a substance that was toxic or dangerous in a general sense. So its like saying radiation is toxic. You wouldn't speak about 'radiations' but talk about radiation being toxic. So while 'radiations' is technically correct we as speakers of English don't use that plural.
The ancient speakers of Latin similarly didn't use a plural form of virus, so when people pluralize it using the rules of ancient Latin they come off like Bush speaking of the internets: they don't know WTF they are talking about but would like to sound as though they do. Sigh. At least its better than when he talks about nucular power.
(Note I said 'bad science fiction'. That does not imply that the fed shouldn't fund research into making a holodeck. That would be cool.)
Nothing is truly safe... It is all a question of odds. The real question is which you'd rather do, swallow a beaker of this crippled Ebola or have a seatmate on a plane flight with EDRTB? Swallow a beaker of crippled Ebola or be on the Bay Bridge in a 6.0 earthquake centered in the bay area? Swallow a beaker of Ebola or go a month without wearing a seatbelt? If TFA accurately portrays the research done, I'd pick the former each time.
They developed a monkey kidney cell line so that they produced a protein that is foreign to primates, and otherwise wouldn't ever be found in a monkey or human cell. So unless you've been genetically engineered to make an Ebola virus protein in your kidneys, I think you'll be safe.
Then get off my lawn.