Category: Medicine
FDA Tiered Approval
Jacob J. Gottlieb and Joseph Gulfo have an interesting op-ed on a tiered approval regime for the FDA:
Instituting a codified approval paradigm based on four tiered levels of clinical effectiveness (biomarkers, clinical signs and symptoms, disease modification and clinical outcomes) — with evidence regarding clinical utility progressively increasing — would greatly reduce the regulatory uncertainty and subjectivity, as well as the time to approval of innovative medicines.
Moreover, the four tiers, coupled with a commitment to apply state-of-the-art technologies (Apple Watch, telemetry and other health monitoring systems) to obtain clinical evidence would allow for additional learnings from use of drugs by practicing doctors treating real world patients. This knowledge would unearth additional uses, information that can be added to the product label to allow safer and more effective use of drugs and the identification of drug combinations that lead to even greater health benefits.
See also Bartley Madden’s work on Free to Choose Medicine which would similarly create dual tracks, one the standard FDA process and a second observational track that would bring drugs to market more quickly with the tradeoff being fewer clinical trials. As clinical trials rise in expense and more treatments are targeted towards smaller patients groups (i.e. personalized medicine) and as statistical techniques improve, we will need and can benefit from reforms to the FDA process along these lines.
Amazon bans some anti-vaccine books
Amazon has now joined other companies navigating the line between doing business and censoring it, in an age when, experts say, misleading claims about health and science have a real impact on public health.
NBC News recently reported that Amazon was pulling books touting false information about autism “cures” and vaccines. The e-commerce giant confirmed Monday to The Washington Post that several books are no longer available, but it would not release more specific information.
I cannot say I am entirely happy about that (grossly underreported) development. Here is the full WaPo story by Lindsey Beyer.
Opioids and the Labor Market
Do not believe those who tell you the only labor market problems have been demand side!:
This paper studies the relationship between local opioid prescription rates and labor market outcomes. We improve the joint measurement of labor market outcomes and prescription rates in the rural areas where nearly 30 percent of the US population lives. We find that increasing the local prescription rate by 10 percent decreases the prime-age employment rate by 0.50 percentage points for men and 0.17 percentage points for women. This effect is larger for white men with less than a BA (0.70 percentage points) and largest for minority men with less than a BA (1.01 percentage points). Geography is an obstacle to giving a causal interpretation to these results, especially since they were estimated in the midst of a large recession and recovery that generated considerable cross-sectional variation in local economic performance. We show that our results are not sensitive to most approaches to controlling for places experiencing either contemporaneous labor market shocks or persistently weak labor market conditions. We also present evidence on reverse causality, finding that a short-term unemployment shock did not increase the share of people abusing prescription opioids. Our estimates imply that prescription opioids can account for 44 percent of the realized national decrease in men’s labor force participation between 2001 and 2015.
The fact that the demand side blade of the scissors can be powerful does not imply the supply side blade does not matter, no matter how many snide tweets you may read to the contrary.
The paper is by Dionissi Aliprantis, Kyle Fee, and Mark E. Schweitzer at the Cleveland Fed.
Via Ilya Novak.
Bring Back the FDA’s Parallel Track
In 1992, the AIDS/HIV “parallel track” was approved as a regulatory change for FDA to allow patients exclusive access to AIDS/HIV drugs that had passed safety tests but had not yet passed all efficacy tests. Other drugs did not have access to this approval option. As a result of parallel track, the highly effective anti-viral drug stavudine was approved, saving thousands of lives.
…In the years that followed, FDA and Congress created several paths to speed approval and open access to promising medications, including accelerated approval, priority review, fast track, breakthrough therapy, right to try, and expanded access, or “compassionate use.” Unfortunately, these approaches are often confusing, and it is difficult for drug developers to determine which approach to pursue. None of these reforms have matched the openness and simplicity of the parallel track…
Ed Hudgins in How Extending the AIDS Drug Access Model to Other Diseases Would Save Lives.
Theranos was Fraudulent, What About Its Patents?
In Launching the Innovation Renaissance I argued that patents should be given for specific inventions rather than just for broad “ideas”:
Thomas Edison invented and patented numerous products: the light bulb, the phonograph, movie film and much else besides. (At one point the patent office required that patents be accompanied by working models.) The invention of products typically requires the expenditure of sunk costs in a way that the creation of ideas does not. Today it is not necessary to implement an idea to patent it, and many patentable ideas are so broadly phrased that they could not be implemented in a model.
Edison famously said that “genius is one percent inspiration, ninety-nine percent perspiration.” A patent system should reward the 99 percent perspiration, not the 1 percent inspiration. In inventing the light bulb, for example, Edison laboriously experimented with some 6,000 possible materials for the filament before hitting upon bamboo. If Edison were to patent the light bulb today, he would not need to go to such lengths. Instead, Edison could patent the use of an “electrical resistor for the production of electro-magnetic radiation,” a patent that would have covered oven elements as well as light bulbs.
Daniel Nazer, who holds the Mark Cuban Chair to Eliminate Stupid Patents at the Electronic Frontier Foundation, points out in an excellent article that giving patents for vaguely stated ideas was exactly the problem with Theranos and its so-called patents.
Holmes found a more receptive audience at the USPTO. She says she spent five straight days at her computer drafting a patent application. The provisional application, filed in September 2003 when Holmes was just 19 years old, describes “medical devices and methods capable of real-time detection of biological activity and the controlled and localized release of appropriate therapeutic agents.” This provisional application would mature into many issued patents. In fact, there are patent applications still being prosecuted that claim priority back to Holmes’ 2003 submission.
But Holmes’ 2003 application was not a “real” invention in any meaningful sense. We know that Theranos spent years and hundreds of millions of dollars trying to develop working diagnostic devices. The tabletop machines Theranos focused on were much less ambitious than Holmes’ original vision of a patch. Indeed, it’s fair to say that Holmes’ first patent application was little more than aspirational science fiction written by an eager undergraduate.
…Two legal doctrines are relevant here. The “utility” requirement of patent law requires that the invention work. And the “enablement” requirement means that the application has to describe the invention with enough detail to allow a person in the relevant field to build and use it. If the applicant herself can’t build the invention with nearly unlimited time and money, it does not seem like the enablement requirement could possibly be satisfied.
The USPTO generally does a terrible job of ensuring that applications meet the utility and enablement standards.
Despite never having built a working product, Theranos accumulated hundreds of patents. These patents are now the only thing of value left but the patents aren’t valuable because of breakthrough science, the patents are valuable because they can be used to force people who do breakthrough science to cough up part of their return.
As Nazer puts it:
Accused of having lied to investors and endangered patients, the company leaves us with a parting gift: a portfolio of landmines for any company that actually solves the problems Theranos failed to solve.
Hypnotist markets in everything
Those new service sector jobs:
This hypnotist charges half a bitcoin for helping you remember your lost cryptocurrency password…
“If you’ve got, you know, $100,000, $200,000, $300,000 worth of bitcoin in a wallet and you can’t get access to it, there’s a lot of stress there,” he says. “So it’s not just as simple as saying, okay, we’re going to go do a 30-minute hypnosis session and enhance your memory.”
Miller declined to specify the exact number of participants in his bitcoin password recovery program or how much money he’s recovered, citing client confidentiality. However, he says that there are currently “several people” in his program, who are experiencing varying degrees of success.
Generally, a person who created their password more recently will have an easier time unlocking this memory, he says. Likewise, a client who is feeling low stress will have an easier time remembering their password than one under high stress.
Miller is located in Greenville, South Carolina.
For the pointer I thank Nick Glenn.
Injectable NanoParticles Let Mice See Near InfraRed!
Wow! This paper, Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantenna, newly published in Cell seems like something from the future. Basically they injected nano-particles that convert near infra-red to visible light into the retinal layer of the eye in mice enabling the mice to see in the near infra-red.
…we developed ocular injectable photoreceptor-binding upconversion nanoparticles (pbUCNPs). These nanoparticles anchored on retinal photoreceptors as miniature NIR light transducers to create NIR light image vision with negligible side effects. Based on single-photoreceptor recordings, electroretinograms, cortical recordings, and visual behavioral tests, we demonstrated that mice with these nanoantennae could not only perceive NIR light, but also see NIR light patterns. Excitingly, the injected mice were also able to differentiate sophisticated NIR shape patterns. Moreover, the NIR light pattern vision was ambient-daylight compatible and existed in parallel with native daylight vision. This new method will provide unmatched opportunities for a wide variety of emerging bio-integrated nanodevice designs and applications.
…In summary, these nanoparticles not only provide the potential for close integration within the human body to extend the visual spectrum, but also open new opportunities to explore a wide variety of animal vision-related behaviors. Furthermore, they exhibit considerable potential with respect to the development of bio-integrated nanodevices in civilian encryption, security, military operations, and human-machine interfaces, which require NIR light image detection that goes beyond the normal functions of mammals, including human beings. Moreover, in addition to visual ability enhancement, this nanodevice can serve as an integrated and light-controlled system in medicine, which could be useful in the repair of visual function as well as in drug delivery for ocular diseases.
The researchers are mostly from China. It sometimes seems that Chinese researchers are naturally extropian, bolder and more optimistic about technology, human extension and the future than anyone else in the world.
Hat tip: Paul Kedrosky.
The Impact of the Affordable Care Act: Evidence from California’s Hospital Sector
The Affordable Care Act (ACA) authorized the largest expansion of public health insurance in the U.S. since the mid-1960s. We exploit ACA-induced changes in the discontinuity in coverage at age 65 using a regression discontinuity based design to examine effects of the expansion on health insurance coverage, hospital use, and patient health. We then link these changes to effects on hospital finances. We show that a substantial share of the federally-funded Medicaid expansion substituted for existing locally-funded safety net programs. Despite this offset, the expansion produced a substantial increase in hospital revenue and profitability, with larger gains for government hospitals. On the benefits side, we do not detect significant improvements in patient health, although the expansion led to substantially greater hospital and emergency room use, and a reallocation of care from public to private and better-quality hospitals.
That is from a new NBER working paper by Mark Duggan, Atul Gupta, and Emilie Jackson.
Does “putting yourself in the shoes of others” reduce attitude change?
From Rhia Catapano, Zakary L. Tormala, and Derek D. Rucker:
Counterattitudinal-argument generation is a powerful tool for opening people up to alternative views. On the basis of decades of research, it should be especially effective when people adopt the perspective of individuals who hold alternative views. In the current research, however, we found the opposite: In three preregistered experiments (total N = 2,734), we found that taking the perspective of someone who endorses a counterattitudinal view lowers receptiveness to that view and reduces attitude change following a counterattitudinal-argument-generation task. This ironic effect can be understood through value congruence: Individuals who take the opposition’s perspective generate arguments that are incongruent with their own values, which diminishes receptiveness and attitude change. Thus, trying to “put yourself in their shoes” can ultimately undermine self-persuasion. Consistent with a value-congruence account, this backfire effect is attenuated when people take the perspective of someone who holds the counterattitudinal view yet has similar overall values.
Yes, yes the replication crisis. Still, this may be a useful countertonic against the notion that trying to understand other people always yields high returns. Perhaps the better approach is simply to drain yourself of values when considering the perspectives of other people.
Philanthropic hospital markets in everything
Nonprofit hospitals across the United States are seeking donations from the people who rely on them most: their patients.
Many hospitals conduct nightly wealth screenings — using software that culls public data such as property records, contributions to political campaigns and other charities — to gauge which patients are most likely to be the source of large donations.
Those who seem promising targets for fund-raising may receive a visit from a hospital executive in their rooms, as well as extra amenities like a bathrobe or a nicer waiting area for their families.
Some hospitals train doctors and nurses to identify patients who have expressed gratitude for their care, and then put the patients in touch with staff fund-raisers.
…it could make patients worry that their care might be affected by whether they made a donation.
Despite such concerns, these practices are becoming commonplace, particularly among the largest nonprofit hospitals. A 2016 survey of 108 hospitals found that 68 had grateful patient programs, according to the Advisory Board, a consulting firm.
Here is more from Phil Galewitz at the NYT.
Those new (old?) service sector jobs
Nobody ever warns the patients at Pennsylvania Hospital about Pete Schiavo, “The Groin Crusher.”
The first time most people meet Schiavo, they’ve just come out of a coronary procedure and he’s explaining that after the catheters are pulled out of their femoral artery, he’s going to apply pressure to their groin for 20 to 40 minutes to aid in clotting.
Awkward!
Or it would be, if it was anyone else but Schiavo, a gregarious, emotional, wisecracking guy who is all South Philly, even if he lives over the bridge in Jersey now.
Schiavo, 52, was so overwhelmed to learn that reader Sandy Kuritzky, whose husband’s groin he crushed earlier this year, nominated him for this series that he wept tears of joy several times during his interview.
“I know he doesn’t remember me or my husband because he has his hands on so many groins,” Kuritzky said. “But Pete’s attitude with his patients and their caregivers is so upbeat and friendly and caring and funny that it makes a stressful time less stressful and difficult.”
Patients and their families don’t forget the way Schiavo touches them — physically and emotionally. He’s won awards, had money donated in his name, and gets stopped all the time by former patients who want to buy him drinks or dinner.
“I’m holding someone’s groin for 20 minutes, they tend to remember me and nobody else,” Schiavo said. “I tell them: ‘I can promise you two things when I’m done: You’ll never forget my name or my face.’ And they never do.”
Here is the full story, via Dean C.
What should I ask Ed Boyden?
I will be doing a Conversations with Tyler with him, no associated public event. Here is his MIT bio:
Ed Boyden is Y. Eva Tan Professor in Neurotechnology at MIT, associate professor of Biological Engineering and Brain and Cognitive Sciences at MIT’s Media Lab and McGovern Institute for Brain Research, and was recently selected to be an Investigator of the Howard Hughes Medical Institute (2018). He leads the Synthetic Neurobiology Group, which develops tools for analyzing and repairing complex biological systems such as the brain, and applies them systematically to reveal ground truth principles of biological function as well as to repair these systems. These technologies include expansion microscopy, which enables complex biological systems to be imaged with nanoscale precision; optogenetic tools, which enable the activation and silencing of neural activity with light; robotic methods for directed evolution that are yielding new synthetic biology reagents for dynamic imaging of physiological signals; novel methods of noninvasive focal brain stimulation; and new methods of nanofabrication using shrinking of patterned materials to create nanostructures with ordinary lab equipment. He co-directs the MIT Center for Neurobiological Engineering, which aims to develop new tools to accelerate neuroscience progress.
Here are other Ed Boyden links. So what should I ask him?
Ratio of <= 40 to >= 50 scientists funded by the NIH
The dotted line at the top is the Jones-implied ratio of productivity of <= 40 year olds to >= 50 year-olds, as drawn from Figure 1 in this source.
For the construction of this data source I am indebted to PseudoMontaigne. Does it not imply that NIH funding is vastly over-allocated according to the criterion of seniority? Or might this be the rise of the lab system, where the older people are the PIs, and they in turn dole this money out to younger researchers? More middlemen, so to speak. Opinions?
My Conversation with Rebecca Kukla
She is a philosopher at Georgetown, here is the audio and transcript, I thought it was excellent and lively throughout. Here is part of the summary:
In her conversation with Tyler, Kukla speaks about the impossibility of speaking as a woman, curse words, gender representation and “guru culture” in philosophy departments, what she learned while living in Bogota and Johannesburg, what’s interesting in the works of Hegel, Foucault, and Rousseau, why boxing is good for the mind, how she finds good food, whether polyamory can scale, and much more.
Here is one bit:
KUKLA: What’s interesting in Hegel? Okay. You ask hard questions. This is why you’re good at your job, right?
I think Hegel’s fascinating. I think the main idea in Hegel that is fascinating is that any cultural moment, or set of ideas, or set of practices is always internally contradictory in ways it doesn’t notice, that there are tensions built into it. What happens, over time, is that those tensions bubble up to the surface, and in the course of trying to resolve themselves, they create something newer and better and smarter that incorporates both of the original sides.
That was a much more Hegelian way of putting it than I wanted it to come out, basically — the idea that going out and looking for consistency in the world is hopeless. Instead, what we should do is figure out how the contradictions in the world are themselves productive, and push history forward, and push ideas forward, is what I take to be the key interesting Hegelian idea.
COWEN: Michel Foucault. How well has it held up?
KUKLA: Oh, you’re asking me about people I mostly love.
COWEN: But empirically, a lot of doubt has been cast upon it, right?
KUKLA: On the details of his empirical genealogical stories, you mean?
COWEN: Yes.
KUKLA: Yes, but I think that the basic Foucauldian picture, which is — let’s reduce Foucault to just two little bits here. One basic piece of the Foucauldian picture is that power is not a unify-unilateral, top-down thing. Power expresses itself in all of the little micro interactions that go on between people and between people and their environments all the time.
Power isn’t about a big set of rules that’s imposed on people. Power is about all of the little things that we do with one another as we move through the world. All of those add up to structures of power, rather than being imposed top-down. I think that has been, at least for me and for many other people, an incredibly fertile, productive way of starting to think about social phenomenon.
The other bit of the Foucauldian picture that I think is incredibly important is the idea that a lot of this happens at the level of concrete, fleshy bodies and material spaces. Power isn’t sets of abstract rules. Power is the way that we are trained up when we are little kids — to hold our legs in a certain way, or to hold our face in a certain way, or to wear certain kinds of clothing. Power is the way that schools are built with desks in rows that enforces a certain direction of the gaze, and so on.
I could go on and on, but the way that the materiality of our bodies and our habits and our environments is where power gets a hold, and where our social patterns and norms are grounded, rather than in some kinds of high-level principles or laws, is also, I think, very fertile.
That’s independent of the details of his genealogical stories. Because, yeah, he does seem to have played fairly fast and loose with actual historical details in a lot of cases.
Here is another segment:
COWEN: Let me start with a very simple question about feminism. What would be a rhetorical disadvantage that many women are at that even, say, educated or so-called progressive men would be unlikely to see?
KUKLA: A rhetorical disadvantage that we’re at — that’s a fascinating question. I think that there is almost no correct way for a woman to use her voice and hold her body to project the proper kind of expertise and authority in a conversation.
I think that there’s massive — I don’t even want to call it a double bind because it’s a multidimensional bind — where if we sound too feminine, sounding feminine in this culture is coded as frivolous and unserious. If we sound too unfeminine, then we sound like we are violating gender norms or like we are unpleasant or trying to be like a man.
I think that almost any way in which we position ourselves — if we try to be polite and make nice, then we come off as weak. If we don’t make nice, then we’re held to a higher standard for our appropriate behavior than men are. I think there’s almost no way we can position ourselves so that we sound as experts. So oftentimes, the content of our words matters less than our embodied presentation as a woman.
Definitely recommended.
Department of Unintended Consequences, American health care edition
In 2010, the federal agency that oversees Medicare, the Centers for Medicare and Medicaid Services, established the Hospital Readmissions Reduction Program under the Affordable Care Act. Two years later, the program began imposing financial penalties on hospitals with high rates of readmission within 30 days of a hospitalization for pneumonia, heart attack or heart failure, a chronic condition in which the heart has difficulty pumping blood to the body.
At first, the reduction program seemed like the win-win that policymakers had hoped for. Readmission rates declined nationwide for target conditions. Medicare saved an estimated $10 billion because of the reduction in hospital admissions. Based on those results, many policymakers have called for expanding the program.
But a deeper look at the Hospital Readmissions Reduction Program reveals a few troubling trends. First, since the policy has been in place, patients returning to a hospital are more likely to be cared for in emergency rooms and observation units. This has raised concern that some hospitals may be avoiding readmissions, even for patients who would benefit most from inpatient care.
Second, safety-net hospitals with limited resources have been disproportionately punished by the program because they tend to care for more low-income patients who are at much higher risk of readmission. Financially penalizing these resource-poor hospitals may impede their ability to deliver good care.
Finally, and most concerning, there is growing evidence that while readmission rates are falling, death rates may be rising.
In a new study of approximately eight million Medicare patients hospitalized between 2005 and 2015 that we conducted with other colleagues, we found that the Hospital Readmissions Reduction Program was associated with an increase in deaths within 30 days of discharge among patients hospitalized for heart failure or pneumonia, though not for a heart attack.
That is by Rishi K. Wadhera, Karen E. Joynt Maddox and Robert W. Yeh in The New York Times.