A Brief Update on Adult Stem Cells

Readers of The New York Times and other news outlets may have seen the May 17 announcement that Prochymal, an “adult” stem cell-related therapy to treat children with graft-versus-host disease, was approved in Canada by Health Canada (which is what they call their FDA up there). This treatment, which is made by a company called Osiris Therapeutics, is being tested for other medical conditions. Success does not appear to be uniform, which is to be expected. Most new medical treatments fail in at least some envisioned applications.
Graft-versus-host disease is a complication of transplantation—usually, as in this case, bone marrow transplant—in which immune-competent cells in the donated graft attack the tissues of the recipient. A little bit of this may be tolerable or even desirable, medically speaking, but too much is not pretty. The cells in Prochymal are so-called “mesenchymal” cells, derived from bone marrow. That is, they are in the marrow but are different from the cells, also in the marrow, that are destined to make mature blood cells. They are obtained from healthy adult bone marrow donors and are made into a treatment that can be prescribed “off the shelf,” so you don’t have to find new donors every time you want to use them. That is a neat technical feat.
Recall that somatic or “adult” stem cells are found in different tissues of the body and have different abilities to be transformed into some other kind of cell. They can’t make a whole individual. Readers of this blog will recognize them as the “good guys” of stem cell research and therapy.
This treatment is not yet approved in the U.S. I suppose it might be in the future. It seems to have followed a pretty standard scientific, ethical, and regulatory paradigm for the development of new drug and biologic treatments.
Most, but not all, adult stem cell treatment involves stem cells that specifically exist to form blood cells, for use as bone marrow transplants. These cells can come from a donor’s bone marrow, or they can be filtered out of the blood stream, where they circulate, or, increasingly, they come from umbilical cords. These historically have been used by medical centers as a procedure, but central banks are arising to procure, store, and provide them. Accordingly, the FDA is regulating them more and more as products like drugs.
There is ONE such adult stem cell product approved by the FDA—Hemacord, which consists of umbilical cord cells. There are late-stage trials seeking to establish that adult stem cells from bone marrow are useful in treating heart failure, for example, but to my knowledge final results are not yet available.
There are also a number of efforts to use people’s own adult stem cells for them—for example, in plastic surgery. FDA regulations require that this use be limited to cases where there is “minimal” manipulation of the cells, and the threshold for “minimal” is being fairly hotly disputed. If it is exceeded, FDA asserts substantial control over the efforts—at substantial effort and expense for the practitioners. I believe this is what much of the recent hubbub in Texas over adult stem cell treatments is about, but this blog is not big enough to delve deeply here.
I will say I think we should be careful about “scoreboards” of successes with adult vs embryonic stem cells. I find them misleading at best. If we are counting individual cases, that is not the same as approved therapies, and the number of individual successes is probably too low on the adult side without including the thousands of successful bone marrow transplants.
But in this context, the application of adult stem cells still appears to be expanding, and milestones like regulatory approvals should be noted by those interested in this area. And that, of course, is before we start talking about newer approaches, like iPSCs, to more “juvenile” stem cells.

Whoa, Robot

This week’s many events include these three: I watched the movie I, Robot for the umpty-umpth time; the FAA announced it will make it easier for domestic agencies (e.g., the police) to fly unmanned drones in the U.S.; and the Wall Street Journal ran this article by Dr. Jonathan Moreno from the University of Pennsylvania: “Robot Soldiers Will Be a Reality—and a Threat.”
Dr. Moreno—well-known to readers of this blog, through Heather Zeiger’s recent series of posts—worries deeply about the confluence of neuroscience and military technology. Some conceivable applications of bleeding-edge neuroscience threaten individual autonomy and public freedom, and write the questions of justice in large letters. As skeptics of human enhancement point out, what is to prevent some future enhanced being, humanoid or not, from taking over from us people? The “dual use” problem—that technologies may be used for good or ill—poses, at the extreme, existential risks to the human race, risks so great that they render “risk/benefit” analysis useless. (Dr. Moreno also made this last point in 2010, before the Presidential Commission for the Study of Bioethical Issues, regarding synthetic biology.)
Brain-machine interface technology, that could help paralyzed people control artificial limbs with only their thoughts, could not only be used to dominate an enhanced human soldier’s mind (as Heather pointed out), but also to permit humans to oversee weapons systems that are increasingly autonomous. Even now, automated systems (without the human brain interface, to be sure) are on duty in the Korean DMZ. But more sinister still is the prospect that experiments in quantum computing will lead to robotic warriors based on “whole brain emulation,” capable of making attack decisions that are out of the control of humans. They could be used to attack innocent people, ignoring the laws of war and honor.
It calls to mind the dystopian logical conclusion of I, Robot’s three laws, and Dr. Lanning’s musings that “free radicals” of code could spontaneously at least mimic the actions of the soul (like intention and self-awareness). The deep questions of philosophy of mind aside (for now), Dr. Moreno recommends lots of urgent international negotiations, of treaties, rules, laws, verification systems, human overrides, and the like. He also argues that “fully autonomous offensive lethal weapons should never be permitted.”
He’s right. And yet, for starters, we have a much more “nearfetched” problem at our door: if we allow unmanned surveillance drones flying around our communities, even in the name of only watching for the bad guys, we accept the use of an instrument of war over our people. Let’s start by banning that. It’s tempting, when we look at the places where the police seem outgunned, but we should advocate a ban on domestic drones, as well. (What’s that, guns are also an instrument of war? Not like drones, they’re not—anybody hunt deer with a drone?)
To get around to it, my points: 1) It is time now to stand, on a lot of fronts, and say “we shall not”; 2) Support Dr. Moreno’s negotiations, but realize that no set of rules will buy complete security, that bad actors will persist, and that the situation is so complex that useful rules will be elusive (how’s that Dodd-Frank regulation writing going?); 3) Aggressively defend the so-called “medical boundary”—technology should be used to heal disease, not do “extra-human” things. It’s not a bright line, but a useful concept nonetheless; 4) Accept—and here’s where it gets really hard—that there is such a thing as a normative, or essential, human nature, that establishes boundaries that ought never be violated (probably a position inaccessible in any meaningful way to the atheist/naturalist); and 5) Consider moving the “ban boundary” into the laboratory. In this case, why should we be doing experiments in quantum computing? What legitimate, God-honoring purposes are being served? The scientists should be pressed, hard, to articulate goals.
In the meantime, I wonder if I should take cover….

Pondering On the Way to the Biobank

Personalized medicine is all the rage these days. Much too big a waterfront to cover here, and, as is so often the case, one must be clear how one is defining “personalized medicine.” Often, the application is relatively straightforward; for example, does a person’s particular disease have a feature that makes him or her more likely to respond to a “targeted” new drug? (See Kalydeco for cystic fibrosis, or vemurafenib for melanoma, for two.) Efforts like this are not simple, but relatively uncomplicated.
But often, “personalized medicine” refers to a much more ambitious—and still distant—project: sifting through patterns in people’s entire genomes—all 30,000 or so genes—and discerning something akin to a “fingerprint” that can be used to predict the likelihood of getting a disease, preventing a disease, or responding to treatment. An article in the February 2012 issue of Nature Biotechnology looked at this: “Personal medicine—the new banking crisis” was its title.
It’s now possible to have a machine “read” the entire sequence of all of someone’s genes in a matter of hours for a cost of about $3000. $1000 or less is on the way. A number of major biobanks, consisting of non-profit, academic, and/or government entities worldwide, are collecting people’s samples (blood or other diseased or healthy tissue), and their genomes, in big databases that are analyzable (by really sophisticated computers), with the data sharable. One of the biggest, Généthon in Paris, has banked “300,000 samples from 80,000 people with 400 genetic disorders,” according to the aforementioned article. The first idea is to analyze large groups of people and genes; only later would, it is hoped, the results be able to guide treatment of individuals.
Practical issues include ensuring that the samples are actually usable, that the results from individual tests are reliable, and that there aren’t mixups of samples. But consider also:
• How will any audits/changes in the data be controlled? How can physicians or others trust the results?
• Establishing relevance to any clinical condition requires linking to medical records, electronically to be sure. Yet, reliable and efficient electronic medical records are hardly a reality, in general, as of today. Without the link, one has the specter of “the $1000 genome and the $1,000,000 interpretation.” And we don’t know what genome patterns, if any, may make a big difference in the health of individuals.
• Given that, there is great risk of individuals assuming they can have their healthcare guided by reading their genes, and there are people who would sell that idea to them, today. This is overselling; it’s not ready yet.
And some of the ethical issues are:
• Keeping the information confidential. Current privacy laws may not apply to genetic information. Also, the standard is to “de-identify” specimens so an individual cannot be associated with the genetic test results. But breaches of confidentiality can and do occur, and, eventually, some “re-identification” will be desired if results are to be used for a person’s medical care.
• What constitutes proper informed consent? How much must someone be told about the testing? And what limits must the researchers accept on future testing? In one case, a Native American tribe objected when specimens they thought were to be used for diabetes testing were later used to study genetics of mental illness ancestry, in violation of their values. What if a finding is made that might be clinically significant? Is it required, desirable, or even possible to inform someone of his or her individual result from a biobank’s testing? Is implied consent, or use of an “opt-out” approach, acceptable?
• What are the rules for sharing of specimens or data between groups of scientists? Or across national borders?
• How will discrimination be avoided?
• Should people retain some interest in any commercializable results from testing of their specimens?
Those are for starters. The Presidential Commission for the Study of Bioethical Issues (http://www.bioethics.gov/) is currently looking at the ethical ramifications of large scale human genome sequencing, and has asked for public comment up through May 25. Follow this link for the announcement: http://bioethics.gov/cms/node/676. If you wish to comment, you may do so at [email protected], or by mail to an address provided in the announcement.

Human Dignity on the Cancer Cost Curve

I apologize for the grandiose title…
If medical care simply must cost less than it does now, and if one is concerned that the goals and values of sick patients will be steamrollered by opinions of small groups of experts, where might things be headed? One view that the experts—i.e., doctors—may do some things to keep outstanding care affordable and in the best interest of the patient was proffered in May 2011 by Drs. Thomas Smith and Bruce Hillner, in their article, “Bending the Cost Curve in Cancer Care,” in the New England Journal of Medicine.
Drs. Smith and Hillner proposed that oncologists change their attitudes and practices in 10 ways. I condense and summarize them here; while all seem eminently reasonable to me on their face, some may raise tensions for human dignity, if that is understood from the perspective of patient choice. The condensed list:
1) Test cancer patients who are in remission less frequently for recurrence.
2) For most advanced cancers, use less chemotherapy—fewer cocktails of several drugs, at lower doses (rather than toxic doses with expensive other drugs to mitigate the toxic effects), stop giving chemotherapy after 3 rounds of failure, and don’t give chemotherapy to bedridden patients.
3) Integrate supportive care, of the sort usually identified with hospice in the last days of life, earlier on, with active treatment.
4) Pay doctors more for end-of-life conversations and other treatment planning, and reduce their financial incentives to overtreat. (Many cancer doctors make half of their incomes giving chemotherapy.)
5) Accept that cost-effective analysis and limits on availability/allocation of some treatments are here to stay.
6) Both doctors and patients should adopt more realistic expectations (we tend to be over-optimistic about how well active treatments will work).
7) Patients with [advanced] cancer should have end-of-life discussions with their doctors fairly early on in treatment.
Of this list, the first three are supported by a growing corpus of medical evidence. The next two are policy matters that raise ethical issues (doctors’ values, rationing). I think all 5 are coming, regardless of whether our government’s policies are more “Democrat” or “Republican” going forward. Policy questions in particular demand the broadest public discussion, as Dr. Dan Sulmasy and others have argued elsewhere.
The last two are the most poignant, because they sound sort of defeatist but they go to how we think about, and how much we cling to, our earthly lives. They demand intimate conversations in relationships characterized by trust and the covenantal role of the physician. Our medicines can often do much, but they can’t do everything. Of course, the Christian’s eternal hope provides critical context for these concerns.
Any affront to the dignity of “do everything” autonomy can be more than offset by the dignity of physicians wisely providing the best care they can to their patients, and guiding their patients through the necessary decisions. But those decisions must remain as individualized as possible. A list of broad principles does not distill into an easy formula or blanket rule. And setting appropriate expectations need not collapse into “rationing at the bedside.” Still, it may be critical to remember—to turn around Dr. Robert Orr’s statement—that “we never withhold care, but we may withhold treatment.”

Expertocracy, Paternalism, and “socializing” health care costs

If you haven’t already surmised, I confess it—the Wall Street Journal is my newspaper of record. (Apologies to the half of the country that prefers the New York Times.) Last Saturday’s WSJ review section carried a piece by Drs. Pamela Hartzband and Jerome Groopman of Harvard, decrying the “Rise of the Medical Expertocracy.” These two—particularly Dr. Groopman—have been writing thoughtfully about medicine for a while.
Their point: policy makers and citizens, regardless of whether they say they favor government or private-sector approaches, agree that all our health questions can and should be answered by the right panel of experts. It’s just a matter of whose experts we choose. Democrats have the Independent Payment Advisory Board, Republicans have insurance companies and their experts. Either way, the experts will “Figure out what works, and what doesn’t…pay for value and empower consumers…[and] no one will come between us and our doctors.”
Touche.́ I certainly have argued for so-called “best practices” in this blog. But these two doctors point out that expert opinions often conflict, outcomes cannot be guaranteed, rational patients do not make decisions primarily based on data, and “much of medicine still exists in a gray zone where there is not one right answer.” Moreover, “beyond safety protocols, there is scant evidence that [‘best practices’] improve our health.” What we are left with, they argue, is an objectionable new form of paternalism, when we should be emphasizing clinical decisions that are “based on a patient’s goals and values.”
These points are all well-taken and mostly correct. Where I would push back:
1) It seems to me that there IS a place for some clinical trial-driven “best practice” research, particularly regarding high-cost technologies of unproven or dubious value, where physicians have an (inappropriate) incentive to use them, either because entrepreneurship gets in the way or reimbursement rules are misplaced (see also the posts by Joe Gibes on Feb 17 and Steve Phillips on Feb 22);
2) It also seems to me that there is broad agreement that we should “socialize,” or share, at least the most egregious medical costs across large groups of people—whether through “public” or “private” options. We Americans are haggling over the most prudent and just way to do that. But what if the patient’s goals and values differ from others sharing the costs, not just regarding matters that most readers of this blog would consider moral concerns (e.g., paying for abortions), but also regarding questionable treatments? For example, I’m not so sure I’m willing to pay for someone else to receive Avastin for breast cancer, outside of a clinical trial. I don’t think it works. At some point, “We’re not paying for that” seems inevitable.
I suspect this new paternalism is here to stay. It may be soft, or not so soft. How much of it should we accept?

Post-Mortem Conception and Theology of the Body

This item from yesterday’s news: the courts are considering whether infants, born to a mother after having been conceived in vitro using the banked sperm of her late husband, qualify for federal survivor’s benefits.
The news report included this: More military men are banking sperm so that, in the event of their demise on the battlefield, their widows may start or enlarge their families after they are gone.
I can’t comment on the points of law here. But the whole situation seems amiss from the get-go.
“Repugnance” doesn’t apply, as I see it. It’s kind of easy to sympathize with the underlying sentiment. And this is not like T.S. Garp’s mom. Remember her? “I didn’t want his love, I only wanted his sperm.”
But I submit we should not embrace this practice, but gently challenge it. It deliberately brings children into the world who are, at least for a time, fatherless. And it forgets that children are properly begotten, borne, and raised by the living union of man and wife, and the fruitfulness of their intimacy, their oneness. To be sure, the ravages of war do great violence to this, and we should bemoan and, as much as we can, combat that violence. Still, it seems to me that there is not so much a limit to be observed here as there is a truth to be reaffirmed and celebrated.
That truth is that the procreative and unitive aspects of our sexuality must be held together—or, maybe, reunited—within the boundaries of living, biblical, covenant, heterosexual marriage. It is part of the created order that ought to be treated as a “given” of our lives, and not violated.
More generally, I think that this case reminds us that we must articulate an overall “theology of the body,” as noted by Paige Cunningham in the current issue of Dignitas. (Ooh, I’d better renew my CBHD dues!) I, a layman, and still a learner in bioethics, am not the best person to lay out the tenets of this theology. (So, help me out in the comments.) Some seem straightforward enough: All is not one; the Creator is metaphysically distinct from the creation. We are bodies and souls in union. (Gnosticism and naturalism are both pagan at heart.) Godly sexuality is to be enjoyed. Babies come from that joy, not just from “sperm and egg.” We don’t have children so that we can, somehow, “live on” in them.
Other tenets may be easier to say, but, for me anyway, harder to grasp at a deep, intuitive, emotional level. First, as important as human flourishing is, it is subordinate to eternal joy. I’ll speak for myself: I think I lead too quickly with human flourishing in some of my bioethics arguments. Maybe “What does it mean to flourish as a human being?” is not the best question. Maybe, “What does it mean to glorify God and fully enjoy Him?” should come first, and a bit louder.
Second—and I’m trying to get at this afresh in contemplating the cross—it’s both critical and hard fully to appreciate the incarnation. For one, do we believe in the supreme human excellence of Jesus in His humanity, as, for example, Dallas Willard pressed in The Divine Conspiracy? For another, how do we get at Jesus as “altogether lovely,” “our Beloved,” as the allegorical readers of the Song of Solomon, for example, encourage?
And finally, while I’m at it: We are not our DNA. I can’t emphasize this enough. We are more our souls, or at least our ensouled bodies, than our DNA. I urge readers of this blog to eschew sloppy popular phrases that seem to identify our DNA with our identity. For example, please don’t go around saying things like, “It’s in my DNA,” unless you are talking about a specific trait that really IS. And be careful about resting too heavily on genetic endowment in discussions of human nature.

A bit more about drug shortages

Critical shortages of essential drugs continue to plague American medicine. My email inbox includes a daily update from the FDA with, among other things, the latest status reports on drugs in short supply. There were 24 on today’s list. The cancer drugs Doxil and methotrexate were not described; you may have seen that the FDA recently announced some stopgap measures to permit importation of substitutes for those drugs.
For people with cancer, that was a bit of welcome news, but sometimes a substitute won’t do. Pinch-hitting for Doxil, for example, is a drug called LipoDox, which is similar but not the same thing. The differences could be important for patient outcomes—especially for patients in clinical trials using Doxil. Those trials are on hold; the possibly different results with a substitute could make a whole trial uninterpretable.
Most of the drugs in short supply are, in fact, generic, and they generally are not pills but drugs that have to be provided and administered under sterile conditions, by vein. That makes them challenging to produce, and one hiccup in a pharmaceutical plant can ruin their whole day—or a few weeks or months while they shut down and fix things. That has happened to big producers like BenVenue and Teva.
The clearest ethical issue is the appearance of gray markets, consisting of some distributors who exploit shortages to charge larcenous prices. Investigations into these gray markets are ongoing. For example, an outfit called the Premier healthcare alliance has published reports in the last few months. (They don’t publish the names of the reportedly price-gouging vendors.) Drug manufacturers on one end, and hospitals on the other, are on the lookout for these gray market operators, and they say they are aggressively trying to avoid them. Price is not the only issue—drug counterfeits may be involved, as well.
Some weeks ago, a post on this blog raised the ethical issues of allocating scarce resources with regard to these drug shortages. That is, of course, salient, yet less interesting to me. Why? Because, as M.D. Anderson Cancer Center’s Dr. Hagop Kantarjian has put it, drug shortages are “a preventable human disaster.” We should be able to fix this problem.
How? Condemning the gray marketeers is generally agreed upon. But some would go further and say that enforcing price controls is the principal answer. In fact, relaxing those controls may be a better choice. Medicare and Medicaid pay “average wholesale price” plus 6% for these drugs, which are generally cheap. Professor Awi Federgruen of Columbia Business School recently argued in the Wall Street Journal that allowing producers to charge a bit more for these effective drugs would increase the incentive for more suppliers to make them and make the investments needed to be sure their plants avoid shutdowns.
Also, while there’s no lack of finger pointing toward manufacturers (who need to get their act together) or the FDA (for, supposedly, over-regulating), and while some regulatory adjustments may help, Prof. Federgruen has another suggestion: hire (or contract) more reviewers to reduce a 12-month backlog of applications for new generic drug manufacturing plants and processes. Does anyone else want to join me in saying “Duh?”
Maybe the best approach is less one of moral reflection or enforcement than practical problem-solving, in this case.

Contraception, Conscience, and the Language of War

Outcry over the HHS contraception mandate is not going away—and it shouldn’t. (See Steve Phillips’s excellent February 1 post on this blog.) Now, the press is horrified that social conservatives are being heard with a new vigor in our political discussions. “Can’t we just get along?”
Well. Last fall, the sitting Secretary of HHS told supporters of the National Abortion Rights Action League that “we are in a war.” Here’s a link to a report of that: http://www.ncregister.com/daily-news/sebelius-war-lands-her-in-court/. So, several months before the actual promulgation of the regulation, our government officials—at least as high as the Cabinet, if not higher—openly declared war on religious freedom. When the government—with the power of the sword—says that, it is not unreasonable to assume it means it.
The President’s “accommodation” is, of course, a distinction without a difference. It was pronounced “unacceptable” in a letter announced on February 10; the pdf available online shows today’s date, February 21, and can be linked here: http://www.becketfund.org/unacceptable/ In response to the complaint, “Where are the women?” one might note the women who have signed the letter, including CBHD’s Executive Director, Paige Cunningham.
To be sure, as unavoidable as the language of war is in the policy arguments, it may be a bit harsh on the individual level. I don’t talk nearly as much as I ought with people who disagree on social issues, and some of the venues (e.g., the workplace) are sensitive at best, but I have to remind myself to try to tone it down if I can. (Those who know me know I can come across as pretty arrogant.) I think the main discussion point is that the issue is how much control the government ought to have, NOT the supposed health benefits or general availability of the Pill to those who find its use morally acceptable and want to use it. The even more critical point—touchier to discuss, essential to practice—is the full, rich, cosmic significance of marriage in God’s creation design (cf. Genesis 2:18-25) and His redemptive plan (cf. Ephesians 5:31-33). As many have commented, the two big shots the family has taken below the waterline in my lifetime are the Pill and no-fault divorce—abetting the notion that marriage is principally a contractual arrangement for the benefit of adults.
Still, make no mistake—it’s 1534, and the king wants a divorce. (And, while you’re at it, think also of Russell Hittinger’s argument that, in the French Revolution, the Catholic Church drew its battle line at government control over marriage and the family.) We must be stout and wise in this one.

Is(n’t) Kalydeco Worth It?

You may have seen the news last week that the FDA approved Vertex Pharmaceutical’s Kalydeco™ (ivacaftor), a drug used to treat people with cystic fibrosis (CF) who have a specific mutation of a gene called CFTR. CF is a miserable, inherited disease that afflicts about 30,000 people in the US. It causes stick mucous, making breathing labored, infections frequent, digestive problems the norm, and early death (around age 37) a patient’s destiny. About 4 percent of those have the mutation targeted by Kalydeco, meaning that it will be useful for only about 1,200 people—a true orphan drug. From the data summary in the drug label, and anecdotal reports in the general press, this group of patients improves—sometimes a lot. They feel better, their lungs work better, they get fewer infections, they gain weight. They have to take the drug—a pill—twice daily, continuously. If resistance to the drug has emerged, I am not aware of it—but I’m not an expert in CF.
The drug had been in development since the late 1990’s, first by a venture-backed company, Aurora Biosciences, then by Vertex after an acquisition in 2001. The pivotal clinical trials included 213 of the 1,200 potentially eligible patients—a remarkable effort by the company, the doctors treating the disease, and the patients participating. Clinical trials are not finished; the FDA will require Vertex to do a (small) clinical study to address the potential for certain drug interactions, but that’s not a big hurdle. Also, data are not yet available to show the drug is safe and effective in children under age 6.
The FDA approved it in 3 months after getting the data for review—a true fast track.
Oh, and it will cost $294,000 a year per patient.
On its website, the company advertises a financial assistance program it says (press release dated 1/31/12) includes free drug for people with no insurance and an annual household income of $150,000 or less, and co-payment/co-insurance support for “up to 30% of the list price of the medication,” after “a minimal out-of-pocket obligation,” for people of any income who have insurance. Since insurance co-pays for specialty drugs like this commonly are a quarter to a third of the total price, this sounds like, in effect, secondary insurance from the manufacturer to help people afford it.
I think it’s a good deal. I can’t guess at the details of Vertex’s financial calculations based on the publicly available information I can find. They told the SEC that they had about $1.4 billion in revenue last year, almost all from its approved hepatitis C drug and other payments in their hepatitis C work, and about $190 million in profit. They expect to spend roughly $750 million in the next year on R+D all told. I don’t know how much they spent developing Kalydeco. The San Diego Union-Tribune said “millions of dollars of [Vertex’s] own money.” The Cystic Fibrosis Foundation, which will get royalties from Kalydeco sales, contributed $75 million to the drug’s development.
So, although I can’t fully defend the pricing, it sounds like this drug is worth the price. In thinking about these “expensive drug” questions, I suggest: 1) Realize that drug companies are medically-oriented businesses, not an arm of the medical profession, and therefore subject more to business than medical ethics when it comes to financials; 2) Challenge the too-simple notion that “making all drug companies non-profit” will reduce costs or be beneficial to society, since the issues of financing expensive development and recouping costs do not go away, and non-profits’ operations can be distorted by the actions of sinful/fallen actors; 3) Judge each case on its own, separate merits—Kalydeco sounds to me like a much better value proposition than, say, Avastin for breast cancer did; 4) Resist the Manichean “drug-companies: evil” grunt; 5) Affirm that there is a societal obligation to make effective but expensive drugs available for those who need it. That means that, whatever set of payment arrangements we adopt, I’m all for my tax dollars or insurance premiums being used to get this drug to a stranger who would benefit from it.
I realize that doesn’t magically solve the issues raised by expensive new drugs, but I submit it provides a framework for proceeding.

Getting the Doctors to be the Doctors

Physician readers of this blog probably saw the two-page “viewpoint” piece by Dr. Ezekiel Emanuel in the January 4, 2012 edition of JAMA, under the title, “Where Are the Health Care Cost Savings?” The upshot: “First, physicians must be the leaders and must stop looking to drug companies, insurers, or someone else to initiate and achieve cost savings.” (When I read “someone else,” I think, “government.”) I think there is a lot to this—it’s not just an example of asking physicians to answer to society rather than care for patients, a charge with which Dr. Emanuel is undoubtedly familiar. Consider his reasoning:
• Slowing the growth of health costs means “going where the money is” by identifying approaches that can cut costs by at least $26 billion a year, or 1% of current expenditures.
• That implies improving care of people with chronic conditions like coronary artery disease, diabetes, congestive heart failure, and others. About 10% of the population currently requires about 64% of the costs, and most of the 10% are people with a few chronic conditions like coronary artery disease, diabetes, and the like. These patients would be better served, at lower cost, by concerted efforts to reduce avoidable complications, improve patient monitoring, increase medication compliance, use specialists more efficiently (read: selectively), and use technology and currently-less-reimbursed activities (home visits, lifestyle and transportation services) to achieve these.
• Many popular suggestions for reducing cost would have a low “bang for the buck:”
o Malpractice reform might save $11 billion, or 0.5%, per year;
o Reducing insurance company profits means cutting into an amount that, in 2010, totaled $11.7 billion for the 5 largest insurers;
o Drug reimportation might save $2.6 billion;
o Replacing all brand name drugs with generics would save Medicare Part D less than $1 billion;
o Rationing end-of-life care is similarly misguided—in 2010, only 255 patients nationwide had care costing over $1 million each, and while those with bills over $250,000 add up to 6.5% of health costs, they cannot be identified in advance, so planning good but cheaper care for them prospectively is impossible. Besides that, people would “raise the charge of ‘death panels’”—something else he’s heard before. (Insert the emoticon of your choice here.)
Physician leadership principally means, for Dr. Emanuel, that they must work together to redesign care delivery for chronic illness—a challenge, but “only effective physician leadership can ensure successful redesign.” It also means, however, that physicians should not just accept that they will have to be paid differently (bundled payments rather than fee-for-service), they should take the lead in proposing how that deal would look.
I know, I know—Dr. Emanuel is famously a proponent of the “IPAB,” and the notion that doctors will magically see their way to enlightened new ways to pay them is pretty facile. But I cite this piece to suggest that the core point—the doctors have to be the doctors—is the critical one. It is for the doctors to tell the rest of us—not for us to tell them—how they can best care for us, collectively as well as individually, and to identify and implement best practices for that. It seems to me that, whether the challenge is avoiding unnecessary complications or critically asking whether that expensive, marginally effective new cancer drug is really good for a patient, that we should encourage the medical profession to be out in front here. The challenges are immense, and not new, but can’t strong societal leadership by doctors, in the name of caring for their patients better, be part of a vigorous revived Hippocratism?