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The bundle Unlike many other CMMI experiments, the Comprehensive Care for Joint Replacement (CJR) program was a true randomized control trial in that participation was mandatory in a selection of metropolitan areas and not allowed anywhere else, which allows for an analysis untainted by self-selection bias. In brief the question to be answered was does a 90-day bundled payment for a joint replacement (knee/hip) get better value (improved care and/or lower costs) than the traditional FFS approach? A differences of differences analysis comparing the bundled vs. control arms before and after the intervention finds that the most significant divergence between… Read More

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Genetic trade secrets In 2012, the US Supreme Court decided a case known as “Prometheus” establishing that therapeutic methods based on biomarkers were not patentable – this essentially blocked one of the two main avenues to monetizing intellectual property from the very hard clinical work of figuring out personalized medicine, i.e. what works for whom. The other avenue that would remain is that of trade secrets, and I for one, have been waiting for the other shoe to drop.  A hint comes from a study on ovarian cancer just published in the NEJM: patients were selected on the basis… Read More

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Peanut medicine that won’t cost peanuts Allergy to peanuts is a major issue and though prevention is now possible in infants there is a huge population for whom actual survival is connected to vigilance in what they consume and availability of epi-pens. Desensitization to allergens is a well-established method to overcome an allergy, but it is typically done through injections, and it requires well calibrated micro-doses of the allergen.  Aimmune has been pursuing an oral approach with progressive dosing with peanut protein (AR101) and in a phase 3 trial, two thirds of the treated patients were able to tolerate… Read More

Posted by on in Digital Health, Medical Devices

Interest and investment in digital health has increased rapidly in recent years.  Some digital health software is impactful enough that it requires FDA approval, but current regulatory pathways are slow and cumbersome for tech companies.  In July 2017 the FDA announced a beta-test of a new pathway, the pre-certification program, which is intended to increase innovation and minimize barriers to market entry for digital health software.  While early signs show the program will have these intended consequences, it also may create an uneven playing field for incumbent players relative to new, smaller organizations.   This is good news for… Read More

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One century after the use of convalescent serum, convalescent T-cells The use of tailored T-cells (e.g. CAR-T) is transforming our approach to (blood) cancers, but what about using T-cells against their raison d’être, intracellular pathogens such as viruses?  JC virus is the cause of Progressive Multifocal Leukoencephalopathy (PML), a fatal disease of the brain triggered by immunosuppression commonly occurring during cancer or auto-immune disease therapy. In a series of three consecutive patients with PML, scientists from MD Anderson infused in the spinal fluid T-cells that had been selected and expanded for their recognition of BK virus (an analog to JC… Read More

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Primary care organizations are better ACOs when it comes to achieving savings Initial results from the Medicare Shared Savings Program ACO have been disappointing pointing to small to negligible net effects on net spending, but a clever analysis digging into the details shows that there is a silver lining. The key insight is to distinguish between ACOs that are health systems and those that are physician practice groups: health systems show no net savings (after bonus incentive payments) while physician group ACOs do. In the physician group ACOs, the savings are driven in roughly equal measure by inpatient care,… Read More

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Transthyretin heats up Last month saw a couple landmark papers about the use of parenteral RNA drugs (from Alnylam and Ionis) in hereditary transthyretin amyloidosis with a focus mainly on mitigating the progression of polyneuropathy. But what matters most for the survival of these patients is cardiomyopathy and although the Alnylam paper did show some impact on that pathology, this was based on exploratory analyses of biomarkers, not pre-specified hard outcomes.  A few weeks later, Pfizer comes out with their oral Tafamidis with clear improved cardiac outcomes including survival, in a placebo-controlled RCT that included not only patients with… Read More

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RNA drugs coming of age Hereditary Transthyretin Amyloidosis (ATTR) is a genetic disease in which one of the alleles of Transthyretin (TTR), a protein produced by the liver and with a role in thyroid hormone metabolism, is mutated resulting in amyloid fiber deposits mainly in nerve and cardiac tissues. Patisiran (Alnylam) and inotersen (Ionis) are both oligonucleotides designed to knock down translation of TTR mRNA, the first through the silencing mechanism, the second through an antisense effect.  Phase 3 placebo-controlled studies published back-to-back in the journal show clear efficacy for both in reducing progression of neuropathy (and sometime improving it). Read More

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It’s hard to quit (and E-cigs don’t help) A large trial (6000 participants) comparing free cessation support, e-cigarettes, and a $600 cash incentive for sustained abstinence shows that none of these approaches are particularly effective with 1-3% overall success rates depending on the arm.  Prevention is where it’s at. A Pragmatic Trial of E-Cigarettes, Incentives, and Drugs for Smoking Cessation (free access)   NPs and PAs numbers are growing fast A look back at the last 15 years and forward to the next 15 shows that the physician workforce is growing at about ~1% per year while mid-level… Read More

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One more on the chin for Alzheimer’s A report of a large phase 3 study of the highly potent oral BACE inhibitor verubecestat (Merck) with yet again a lack of therapeutic effect, despite a dramatic reduction of the cerebrospinal fluid content of beta amyloid in various forms.  With a string of prior failures, this may be the near final blow for amyloid as a treatment target for Alzheimer’s disease (and Biogen’s adacanumab would be the end of the line if it also comes up tails). But note that the study population, although described as “mild-to-moderate”, clearly has sustained substantial brain… Read More