Connection Between Epigenome, Selective Mutability, Evolution, and Human Disease
Li, Harris et al., PLoS Genetics
Researchers at the Baylor College of Medicine and elsewhere propose a "connection between the epigenome, selective mutability, evolution, and human disease" based on the findings of their study on associations of structural mutability with germline DNA methylation and with non-allelic homologous recombination mediated by low-copy repeats. "Combined evidence from four human sperm methylome maps, human genome evolution, structural polymorphisms in the human population, and previous genomic and disease studies consistently points to a strong association of germline hypomethylation and genomic instability," the Baylor-led team writes.
A Buoy Named Sue: Can MDs Navigate Lab-Test Market While Fearing Litigation?
More than half of respondents to a physician survey said they had delayed adopting a "medical innovation" due to fear of being sued. But this same fear could have the opposite effect on lab tests.
This phenomenon may not be a surprise to most physicians or lab pros. And it will only grow in frequency over the next few years as the nation begins to enact Obamacare. Sure it will provide health insurance to nearly every American, but it will also ignore tort reform, which has been among the most vigorous contributors to the rising health-care costs at the center of the reform rationale.
According to the survey, conducted by health-care consulting and staffing company Jackson Healthcare, certain specialties are more likely than others to delay adoption in the future. For instance, 27 percent of pediatricians are least likely to forego new tools, 63 percent of OB/GYNs and two-thirds of surgery subspecialists are most likely. As the survey announcement says, "anything 'new' exposes you to the accusation that you are 'learning' on this patient."
The survey quoted one doc saying he practices “defensive medicine by avoiding the practice of those procedures which might benefit my patients, but are considered too risky by my malpractice insurer and would increase my premiums to a degree that is prohibitive.”
Another, described as a practicing ED physician, admits that he orders between $10,000 and $20,000 worth of "unnecessary tests every day that I work. This is done due to my fear of litigation." That's a single ED doc billing at least $2.6 million a year for superfluous tests. There are around 30,000 ED docs in the US. You get the picture.
This last comment brought to mind a conversation I had with a cardiologist last month, not long after the FDA told Bristol-Myers Squibb to add a black box warning to the label of its anticoagulant Plavix saying that a mutation in the CYP2C19 gene influences how an individual metabolizes the drug.
When I first heard of the label change I thought it could have three possible outcomes: 1) It could encourage physicians to start ordering genetic tests; 2) it could convince them to cling tighter to the status quo; and 3) it could trigger "mass confusion" in their ranks.
As the Wall Street Journal put it, "most doctors aren’t well equipped to do genetic testing. They don’t have quick access to the tests."
The cardiologist with whom I spoke last month, a few weeks after the FDA's announcement, could have added a fourth outcome: Scare the pants off every cardio who prescribes Plavix. BMS sold nearly $1.7 billion worth of the drug during the most recent quarter. That's a lot of bare knees.
This doc, who runs a busy practice in upstate New York, said that when he first got wind of the label change he opted not to alter how he starts or monitors patients on Plavix until more data on genetic testing become available.
He said he has been aware of the FDA's decision in 2007 to add gene-based metabolism data to the label of Plavix's cousin warfarin, and of its move three years later to add PGx-guided dosing ranges to the label. He said he has yet to order a genetic test before starting a patient on warfarin.
Yet he admitted that the new Plavix label caused him some anxiety after he began chatting with colleagues about it — the FDA announced the change on the eve of the American College of Cardiology's annual conference in March — and found that many were equally concerned. (He asked that I not print his name because he does not use genetic tests and doesn't want to worry his patients inadvertently.)
They were made anxious by the same prospect: Of being sued for not ordering a genetic test before starting a patient on Plavix, only to learn that a mutation in that patient's CYP2C19 gene caused him to suffer a drug-induced cardiovascular event.
Since then I've spoken with more than a dozen malpractice lawyers, cardiologists, and bioethicists, and none was convinced that this could happen. There's certainly nothing in the black box that would raise eyebrows.
It does not make genetic testing mandatory. Rather, it says the drug's effectiveness "depends on" a gene and that genetic tests "are available" to identify patients with mutations in it; it describes what might happen to a poor metabolizer prescribed a standard starting dose; and it urges physicians to "consider alternative treatments" for these patients (the FDA says between 2 percent and 14 percent of Plavix users respond poorly to the drug).
The reality is that the
The reality is that the standard of care must be that if one starts a patient on Plavix and fails to order the CYP2C19 genetic test, and the patient suffers an MI caused by a clot because the patient was a poor metaboliser and the Plavix was ineffective and other alternative anti-platelet therapy was not used, IMHO there is absolute liability for malpractice. There is no question in my mind that the FDA's black box warning establishes a standard of care as good if not better than a medical guideline. The warning does not have to be mandatory for liability to attach.