genomeboy.com

Jerome Groopman offers a withering assessment of comparative effectiveness research:

There is a growing awareness among researchers, including advocates of quality measures, that past efforts to standardize and broadly mandate “best practices” were scientifically misconceived. Dr. Carolyn Clancy of the Agency for Healthcare Research and Quality, the federal body that establishes quality measures, acknowledged that clinical trials yield averages that often do not reflect the “real world” of individual patients, particularly those with multiple medical conditions. Nor do current findings on best practices take into account changes in an illness as it evolves over time. Tight control of blood sugar may help some diabetics, but not others. Such control may be prudent at one stage of the malady and not at a later stage. For years, the standards for treatment of the disease were blind to this clinical reality.^[7]

Orszag’s mandates not only ignore such conceptual concerns but also raise ethical dilemmas. Should physicians and hospitals receive refunds after they have suffered financial penalties for deviating from mistaken quality measures? Should public apologies be made for incorrect reports from government sources informing the public that certain doctors or hospitals were not providing “quality care” when they actually were? Should a physician who is skeptical about a mandated “best practice” inform the patient of his opinion? To aggressively implement a presumed but still unproven “best practice” is essentially a clinical experiment. Should the patient sign an informed consent document before he receives the treatment? Should every patient who is treated by a questionable “best practice” be told that there are credible experts who disagree with the guideline?

Amen, Jerry. CER may be well on its way to becoming the “No Child Left Behind” of health care. “Let’s create some immutable standards, wield them like a sledgehammer, and then declare victory!”

Doctors are pooh-poohing personal genomics. Yet they would put their faith in behavioral economics? Talk about going “off label”…

Stephen Asma:

Feeling unworthy is still a large part of Western religious culture, but many people, especially in multicultural urban centers, are less religious. There are still those who believe that God is watching them and judging them, so their feelings of guilt and moral indignation are couched in the traditional theological furniture. But increasing numbers in the middle and upper classes identify themselves as being secular or perhaps “spiritual” rather than religious.

Now the secular world still has to make sense out of its own invisible, psychological drama—in particular, its feelings of guilt and indignation. Environmentalism, as a substitute for religion, has come to the rescue. Nietzsche’s argument about an ideal God and guilt can be replicated in a new form: We need a belief in a pristine environment because we need to be cruel to ourselves as inferior beings, and we need that because we have these aggressive instincts that cannot be let out.

The Presidential Commission for the Study of Bioethical Issues is back and better than ever…we hope:

The commission’s wider scope will also force some tough choices in deciding priorities, says [George] Annas. “Doctors’ [involvement in] force-feeding prisoners at Guantanamo, doctors and torture, and international human-research rules are pressing issues of our day which demand our attention,” he says. Among the other issues he thinks the commission should juggle are new reproductive technologies, an overhaul of informed-consent procedures and — perhaps most immediate — fairer ways to apportion health care. 

To that modest list I’d add achieving peace in the Middle East, ending world hunger, eliminating poverty, curing cancer, and repairing the global economy. I can think of two guys I’d appoint immediately…at least, I think they’re two different guys.

Jenny Reardon on those who choose to opt out:

Only significant effort will achieve the participation of the broader and more diverse range of human beings required for [genomic] research. Understanding why some people participate, and many do not, will demand understanding the specific ways in which genomic ideas and practices form from and re-form social practices of racism and inequality–issues that remain with us despite the last decade of proclamations about the anti-racist and equalitarian features of genomics.

At Nature News, there is something of a eulogy/finger-pointing festival for deCODE and indeed, for personal genomics in general:

…Some other researchers, however, say that deCODE’s scientific approach is to blame. The company worked to mine genetic data for common variations linked to disease through genome-wide association studies (GWAS), and some experts note that these studies have turned up only a small fraction of the variation that causes disease. “The translation to commercial value is just not very direct,” says [Duke’s David] Goldstein, “in part because it is now clear that GWAS is not the tool of choice for unlocking the genetics of most common diseases.”

***

…companies that focus exclusively on personal genomics services, such as the one sold by deCODE as deCODEme, might find themselves in more trouble, [Leerink Swann’s Isaac] Ro says. The services are not seen as a medical necessity, diminishing their appeal, particularly in difficult economic times. This year the personal-genomics company 23andMe, based in Mountain View, California, announced two rounds of lay-offs, lost one of its two co-founders and announced a series of product and price restructurings.

“There’s no clinical trial supporting the value of these results, so it’s really recreational genomics,” Ro says. Large academic centres, not consumers, will find value in the rich genetic databases; 23andMe has tried to move into the research market, but because its data come from a self-selected customer population their value is limited, he says.

Here we go, still trotting out the same tired tropes. I agree: GWAS is of limited value and this probably contributed to deCODE’s demise. But whatever deCODE’s fate, if whole human genomes can be sequenced for < $2000, isn’t it about time we stopped kicking GWAS’s ever-stiffening corpse?  Second, just because something is not a medical necessity, does it follow that it is worthless? Ask the participants in the REVEAL study or anyone else who’s received an APOE genotype because she WANTED to know. Ask the people who learned something about their hereditary breast cancer risk from 23andMe. Is that recreation? What about abacavir hypersensitivity? And finally:  yes, DTC genomics customers are self-selected. So are the 50,000 PatientsLikeMe participants. So are the 10,000 in the Coriell Personalized Medicine Collaborative. So are the 15,000 on the Personal Genome Project waiting list. So are the 400,000 in the UK Biobank. Maybe we should just toss out all of that data, too.

From a compelling story in the New York Times Magazine:

In an age of DNA, when biological relationships can be identified with certainty, it can seem absurd to hew so closely to a centuries-old idea of paternity. And yet basing paternity decisions solely on genetics places the nonbiological father’s welfare above the child’s. Phil Reilly, a lawyer who is also a clinical geneticist, has been wrestling with the policy implications of DNA testing for years, and even he is stumped about how society should manage the problem that men like Mike face. “We’re at a point in our society where the DNA molecule is ascendant, and it’s very much in the public’s consciousness that this is a powerful way to identify relationships,” Reilly says. “Yet at the same time, more people than ever are adopting children, showing that parents can very much love a child who is not their own. The difference here for many men is the combination of hurt and rage over the deceit, the fact that they’re twice beaten. I can see both sides of this argument. As a nation, we’re still in search of what the most ethical policy should be. Every solution is imperfect.”

The Personal Genome Project includes disclosure of nonpaternity as one of the explicit risks of participation. That said, having been warned is probably not much consolation to people who discover certain surprising things about their families.

Elsewhere in this volume she talks about creationism, saying she “didn’t believe in the theory that human beings — thinking, loving beings — originated from fish that sprouted legs and crawled out of the sea” or from “monkeys who eventually swung down from the trees.”

An Italian court has cut the sentence given to a convicted murderer by a year because he has genes linked to violent behaviour—the first time that behavioural genetics has affected a sentence passed by a European court. But researchers contacted by Nature have questioned whether the decision was based on sound science.

***

“90% of all murders are committed by people with a Y chromosome—males. Should we always give males a shorter sentence?” says Steve Jones, a geneticist at University College London. “I have low MAOA activity but I don’t go around attacking people.”

Farahany points out that prosecutors could use the same genetic evidence to argue for tougher sentences by suggesting people with such genes are inherently ‘bad’.

“The question is where do you stop,” Jones adds.

Excerpts from The Federal Register, 7 October 2009 (pdf, but a total page-turner):

Genetic information is defined, with respect to an individual, as information about the individual’s genetic tests or the genetic tests of family members, the manifestation of a disease or disorder in family members of such individual (that is, family medical history), or any request of or receipt by the individual or family members of genetic services. The definition further clarifies that genetic information does not include information about the sex or age of any individual.

A disease, disorder, or pathological condition is manifested when an individual has been or could reasonably be diagnosed by a health care professional with appropriate training and expertise in the field of medicine involved. However, the definition further provides that a disease, disorder, or pathological condition is not manifested if a diagnosis is based principally on genetic information.

GINA’s prohibition on the use and collection of genetic information could increase the potential for adverse selection in the individual health insurance market. Adverse selection arises when individuals seeking coverage have information about their health risks that issuers do not know.

To the extent that GINA and these interim final regulations prohibit group health plans and issuers from incentivizing employees to complete [health risk assessments]  requesting genetic information including family medical history, and response rates for HRAs drop as a consequence, a cost may be incurred that is associated with the forgone benefits of identifying disease risks early and preventing their onset.

The more I read this statute, the less I like it.

“Cancer’s A Funny Thing”

I wish I had the voice of Homer
To sing of rectal carcinoma,
Which kills a lot more chaps, in fact,
Than were bumped off when Troy was sacked.
Yet, thanks to modern surgeons’ skills,
It can be killed before it kills
Upon a scientific basis
In nineteen out of twenty cases.
I noticed I was passing blood
(Only a few drops, not a flood).
So pausing on my homeward way
  From Tallahassee to Bombay
I asked a doctor, now my friend,
To peer into my hinder end,
To prove or disprove the rumour
That I had a malignant tumour.
They pumped in BaSO4
Till I could really stand no more,
And, when sufficient had been pressed in,
They photographed my large intestine.
In order to decide the issue
They next scraped out some bits of tissue.
(Before they did so, some good pal
Had knocked me out with pentothal,
Whose action is extremely quick,
And does not leave me feeling sick.)
The microscope returned the answer
That I had certainly got cancer.
So I was wheeled into the theatre
Where holes were made to make me better.
One set is in my perineum
Where I can feel, but can’t yet see ‘em.
Another made me like a kipper
Or female prey of Jack the Ripper.
Through this incision, I don’t doubt,
The neoplasm was taken out,
Along with colon, and lymph nodes
Where cancer cells might find abodes.
A third much smaller hole is meant
To function as a ventral vent:
So now I am like two-faced Janus
The only* god who sees his anus.
(*In India there are several more
  With extra faces, up to four,
  But both in Brahma and in Shiva
  I own myself an unbeliever.)
I’ll swear, without the risk of perjury,
It was a snappy bit of surgery.
My rectum is a serious loss to me,
But I’ve a very neat colostomy,
And hope, as soon as I am able,
To make it keep a fixed time-table.
So do not wait for aches and pains
To have a surgeon mend your drains;
If he says ‘cancer’ you’re a dunce
Unless you have it out at once,
For if you wait it’s sure to swell,
And may have progeny as well.
My final word, before I’m done,
Is ‘Cancer can be rather fun.’
Thanks to the nurses and Nye Bevan
The NHS is quite like heaven
Provided one confronts the tumour
With a sufficient sense of humour.
I know that cancer often kills,
But so do cars and sleeping pills;
And it can hurt one till one sweats,
So can bad teeth and unpaid debts.
A spot of laughter, I am sure,
Often accelerates one’s cure;
So let us patients do our bit
To help the surgeons make us fit.
                        - J.B.S. Haldane