Blog and Whitepapers
Recon takes an analytical look behind select developments in healthcare
Clinicaltrials.gov and AI-related studies: a brief status check in April 2021
Healthcare is by nature conservative; despite a huge level of interest for artificial intelligence (AI) and machine learning (ML) techniques, significant penetration in standard workflows of care will depend on demonstrations of safety and efficacy. As a result, it is today’s pipeline of clinical studies using AI/ML that will determine mainstream usage tomorrow. In order to better understand this pipeline, we have mined clinicaltrials.gov for characteristics and trends of registered studies making use of AI/ML. Unsurprisingly we see strong growth, but starting from a very small baseline. Although most of
Remodel, rewire, repopulate: an opinionated take on NEJM highlights for April 2021
Remodeling to health? Chronic disease progression is often due to a maladaptive tissue response which leads to remodeling – such as cardiac hypertrophy with hypertension. While most therapeutics focus on tamping down the injury, sotatercept (Acceleron Pharma) in pulmonary arterial hypertension (PAH) breaks new ground by focusing on the remodeling. This modulator of the TGF-beta superfamily looks to inhibit the remodeling of the pulmonary vasculature that worsens the PAH over time, and eventually leads to the demise of most patients. In a 24-week placebo-controlled phase 2 trial (N=106), the pulmonary
Balancing the humors: an opinionated take on NEJM highlights for March 2021
A new approach to schizophrenia Antipsychotic agents treat schizophrenia by manipulating the dopaminergic system. While they are effective at treating psychosis, they can have major side effects and they lack the ability to address so called negative symptoms e.g. apathy, lack of social connection, poverty of thought. Enter the muscarinic cholinergic system which is tricky to manipulate in the CNS without untoward systemic effects as Lilly found out with their M1/4 agonist xanomeline. Karuna Therapeutics has now licensed the molecule and cleverly combined with it with trospium, an antagonist with
How much are Humana’s value-based care models really taking out of utilization?
All that effort for only 0.4% savings Since 2014, HUM has reported on the performance of primary care in value-based arrangements (“VBA”) vs. traditional contracts (“non-VBA”)[1] in Medicare Advantage (MA). One statistic regarding total medical expenditures (TME) is, at first blush, a stunner. The most recent data (2019) shows PMPM TME of VBA members measured only 0.4% less than for non-VBA members. Given HUM’s long-standing strategic commitment to value-based care, commentators are puzzled: is the whole value-based enterprise in vain? does healthcare transformation require quasi-geologic timeframes to deliver meaningful cost
All immunity: an opinionated take on NEJM highlights for February 2021
We can cure Hep C but not immunize against it Sovaldi and other drugs have made curing chronic Hepatitis C a routine, if expensive, proposition. Still, given how common Hep C infection is, and how it can irreversibly damage the liver without overt signs, a vaccine would be highly valuable. Unfortunately, an NIH sponsored trial with a GSK vaccine in 548 IV drug users at high risk of contracting the disease failed to show any protection: 28 participants developed chronic Hep C evenly divided between the placebo and treatment groups.
Walmart Health: Will the fifth attempt at clinics be the charm?
Eighteen months ago, WMT opened its first Walmart Health clinic attached to a supercenter in Dallas, GA. The operation combined multiple services – primary/urgent care, dentistry, behavioral health, optometry, and audiology – with WMT’s Every Day Low Price philosophy (for example, $30 total for a primary care check-up, $40 for a sick visit) in one ~11K sq. ft. site. Boosted by typical supercenter traffic (~5K visits a day is our estimate), and a scarcity of primary and dental care in the local area[1], the clinic got to 2.3K visits-per-month within
While we wait for our shot(s); an opinionated take on NEJM highlights for January 2021
Incremental progress in the fight to treat heart failure After a decade or more of relative quiescence in the 2000s, a volley of new therapies have come to the forefront in the pages of the NEJM: sacubitril valsartan (2014 – Novartis’ Entresto), various SGLT2 inhibitors such as dapagliflozin (2019, AstraZeneca’s Farxiga), vericiguat (2020 – Merck’s Verquvo), and now a 2021 entry from Amgen in the form of the cardiac myosin activator omecamtiv mecarbil. None of those are a panacea, and of the four listed, omecamtiv has the lowest efficacy profile
Closing a tough year: An opinionated take on NEJM highlights for December 2020
Cardiovascular health – go big or go narrow? A follow up on the development of evinacumab (Regeneron), an inhibitor of ANGPLT3 (see this opinionated take from 2017), confirming the safety and LDL reduction effect in a population of individuals with cholesterol levels refractory to other therapies (including PCSK9 inhibitors). Given the history of PCSK9 inhibitors, the development path of this asset will be interesting to follow. Of the 6 trials listed on clinicaltrials.gov not one has anything close to a clinical endpoint – it’s all biomarker based. That will probably
We are back and catching-up: An opinionated take on NEJM highlights for Sep, Oct, and Nov 2020
Small but real progress in ALS: Despite enormous public attention and significant effort, ALS remains a disease for which the development of new therapies has been challenging. Animal models showed potential activity against ALS by sodium phenylbutyrate and taurursodiol, both old (generic) molecules. Now, their effect in combination therapy has been confirmed in a randomized controlled trial. What’s especially interesting is that the effect at 24 weeks (the original duration of the trial) was a modest though statistically significant improvement in functional scores. However, the trial was extended with all
How does OptumCare manage its physician staffing once the big deals are done?
OptumCare’s acquisitions usually make headlines. But what happens when the reporters leave? How is clinical capacity managed? What role do micro-acquisitions, recruiting and retirements play in advancing OptumCare capabilities? This is important because OptumCare is a risk-taking engine. Perhaps by understanding post-acquisition moves, we can reverse engineer United’s view on how clinician capacity and specialty mix can maximize value. We looked at two mature OptumCare geographies, Nevada and Texas with large physician presence and healthy United Medicare Advantage market share (just below 50%). Our analysis primarily uses the Medicare
A tale of two cities: Referral networks of orthopedic surgeons in Miami and Seattle
Summary: We conducted a comparative analysis of the referral networks of orthopedic surgeons in King County (the area around Seattle, WA) and Miami-Dade County. Similarities Bigger systems are better at keeping referrals internal So, the level of fragmentation in the referral base is associated with the level of fragmentation in the specialty market structure Despite this, a consolidated referral base does not necessarily mean that systems are able to keep orthopedics referrals internal Miami-Dade Independent physicians make a significant proportion of referrals (9.4%) So, independent surgeons receive a significant
An ADC renaissance: a resurgence of antibody drug conjugates for cancer
PDF: An ADC renaissance: a resurgence of antibody drug conjugates for cancer Summary: Antibody-drug conjugates (ADCs) have seen a record number of approvals in 2020. This comes after a first era of intense activity in the early 2000s followed by a period of relative quiescence from the late 2000s to mid-2010s. To understand how the nature of the ADC pipeline has changed over time, we have reviewed all 88 ADC oncology programs that have reached phase 2 development and beyond from 1997 onward. We found that, currently, the main contributor
A slow summer: An opinionated take on NEJM highlights for August 2020
A cheap, low tech intervention for a common Achilles’ heel When I am out and about, for instance at the grocery store, I am always surprised at the number of people I see with swollen legs. About half a million times a year in the US, these folks end-up in a hospital bed with cellulitis (a skin and subcutaneous infection) of the leg. In a single center randomized trial with 84 patients who had an episode of cellulitis, an Australian group tested whether compressive stockings would make a difference in
An opinionated take on NEJM highlights for July 2020
Stunting and the microbiome Stunting (low growth for age) affects > 20% of children across the globe and has major impact on the brain, on health, and on opportunities for success in life. The precise mechanism of stunting has remained elusive. Sanitation and diet diversity play a role but targeted interventions in these areas have had less impact than hoped for. Jeff Gordon from WashU has spent the last decade exploring the relationship between stunting and the microbiome, and now his group reports on a study that shows a clear
Covid, medical education, and a bit of RNAi: An opinionated take on NEJM highlights for June 2020
What’s your blood type? The first report of a genome wide association study of Covid-19 severity on approximately 4000 patients and controls conducted in Spain and Italy identifies a locus on the 3rd chromosome that spans 6 potential genes for which polymorphisms appear to drive severe disease. Once the culprit gene is determined, this may help us think about drug targets. Reassuringly the study also recovers the correlation of severity with blood group that has empirically been noted in the past (on chromosome 9 although the signal is not as
AI in healthcare III: COVID-19 applications and implications
COVID-19 has accelerated the adoption of AI in healthcare. AI based tools and solutions can work quickly, be deployed at scale, and respond to the dynamic nature of the crisis. Use-cases span all facets of responding to the pandemic, from diagnosis and triage, to treatment and combating new transmission. A wide range of players—including startups, established companies, universities, and more—are bringing their capabilities and perspectives to the table. Startups like Current Health, a UK-based remote-monitoring company supporting Mayo Clinic and Baptist Health with their COVID-19 response, are benefitting the industry’s
Covid, iPSCs, and ADCs: An opinionated take on NEJM highlights for May 2020
Remdesivir works… but not enough to change the public health perspective The eagerly awaited results of the remdesivir NIH trial are out, and it’s solid but not smashing, although this is a partial read since the study was interrupted before completion because of evidence of benefit (and we should get more data in the coming months). Overall, the primary end-point of faster improvement in the treatment group was met while mortality showed a benefit that was just short of statistical significance. Also important is that remdesivir is clearly safe. But
Buying kit for a leadership position in the @Home revolution? Implications of Optum’s acquisition of naviHealth
Summary NaviHealth is a leader in post-acute care management; since it manages but does not provide care, its impact is constrained by quality of available providers By aligning with Optum clinical and technology assets, naviHealth can raise the capabilities of post-acute providers, direct more cases to be discharged directly to the home and speed up the return home for others Given inpatient stays often mark the start of sustained needs for help in the home, a post-acute navigator like naviHealth could be well-positioned to orchestrate longer-term “aging-in-place” support Overview of
Covid’s backhand blow: payer mix degradation and the threat of renewed payer/provider rate brawls
Among Covid’s many repercussions, the recession shock will drive a sustained degradation of provider payer mix. I estimate that each 5% added to unemployment will incrementally reduce hospital[1] operating margin by 1.0-1.5% and hospitals would need to charge 3-4% more on commercial care to maintain margins[2]. Given that hospital costs make up 40-45% of commercial total cost of care and we are facing unemployment scenarios of 15-20% (per Robert Wood Johnson – see table and source notes), we could ultimately expect this hospital rate pressure – if not averted or moderated
Medicare Advantage’s durable – but underexplained – post-acute care advantage
Health Affairs has put out another study – this one by Skopec and team (subscription access) – comparing post-acute care (PAC) among Medicare Advantage (MA) vs. traditional Medicare (FFS). And, once again (see earlier study here – subscription access), we learn that MA beneficiaries use a lot less PAC than FFS with no major differences in outcomes. The pattern varies by type of PAC: far fewer post-acute MA members spend time in an inpatient rehab facility (IRF) but, when they do, they stay just as long as their FFS counterparts;
Covid and the rest: An opinionated take on NEJM highlights for April 2020
Hydroxychloroquine does not seem to help much in Covid-19 (with caveat) There has been significant attention to the use of the antimalarial hydroxychloroquine in Covid-19, but data on impact has been scarce. In the absence of clarity, New York Presbyterian Hospital left the use of this drug to the discretion of individual treating physicians from mid-March to early April. This has led to two cohorts of Covid-19 patients which can be compared in retrospective analysis: patients treated with hydroxychloroquine (N=811) and those who did not receive the drug (N=565). The
Strategy in the Time of Covid
Preamble A recent post from Recon Strategy outlined the longer-term strategic implications of Covid-19 on 12 healthcare sectors. This post highlights the opportunity to redeploy corporate strategy assets to focus on the most important short-term strategy imperatives to not only ensure organizational resilience but to set up for success coming out of this crisis. Corporate strategy teams have tremendous analytical, creative, and operationally savvy resources that are accustomed to jumping into new situations, getting quickly up-to-speed, and delivering value. Leaders should proactively point these resources towards these areas of greatest
The day after: Implications for hospitals, payers, biotech and more…
Even as our priority today is dealing with the Covid crisis, healthcare organizations would do well to start thinking about the longer-term implications for their strategies. In some instances the marketplace will revert to the prior dynamic, but in many others the changes wrought during this crisis are likely to persist in a way that will call for new strategy or will produce unpredictable outcomes that will require scenario planning. Sectors will be impacted in very different ways and there will be winners and losers in each. In this short
The infectiologists have the floor: An opinionated take on NEJM highlights for March 2020
A first Covid-19 interventional study – unfortunately negative The first of what promises to be a series of many interventional studies for acute Covid-19 disease to appear in the Journal. Lopinavir is an HIV drug that had shown in-vitro activity against SARS, another corona virus, and ritonavir is a drug that boosts lopinavir concentration by reducing its rate of metabolization – so it was worth trying the combo in sick patients with Covid-19. The study was clearly conducted in quasi-battlefield conditions in one of Wuhan’s main hospital from mid-January to
Coronavirus and more: An opinionated take on NEJM highlights for January/February 2020
Keeping up with COVID-19 It’s not easy for a refereed weekly print periodical to keep up with an epidemic that evolves on a daily basis, but the NEJM is doing its best and all articles are free on-line. Most interesting beyond the description of the initial cluster in Wuhan are: (1) the first US case was quite severe and the patient received the antiviral remdesivir (was in development by Gilead for Ebola, but showing activity against coronaviruses) – it is now in testing in China; (2) the rigorous documentation of
Tax dollars doing good work: An opinionated take on NEJM highlights for December 2019
The loneliness of the patent-less drug Colchicine is a very old drug commonly used in gout with an anti-inflammatory mechanism of action that is not well defined. It is a generic (although in the US, the story is somewhat peculiar) and therefore incentives are lacking for further development in new indications by private companies. Given a well-established (but not well-understood) connection between inflammation and cardiovascular events, some researchers have hypothesized and explored potential utility in patients with high cardiovascular risk – but this would have to be validated by a
An opinionated take on NEJM highlights for November 2019
A triumph for cystic fibrosis patients (and for Vertex) Phase 3 confirmation that the benefits seen in early trials from triple-combination therapy of elexacaftor, tezacaftor, and ivacaftor, are sustained and applicable to 90% of the cystic fibrosis patients. Every metric is unambiguously better: sweat chloride concentration, forced expiration volume (FEV1), respiratory symptom questionnaire, pulmonary exacerbations (down 60%), hospitalizations (down 70%). If anything, with 400 subjects, the study was probably overpowered by at least a factor of 4 to show effect. It is great news for CF patients most of whom
An opinionated take on NEJM highlights for October 2019
Genomic applications and scalability Two very different papers about applications of genomics, one for a very common clinical scenario, the other for an ultra-rare disease. It is well known that while clopidogrel (now available as a generic but branded as Plavix) is an excellent antiplatelet agent for a majority of patients, it works poorly in some due to individual genetic idiosyncrasies of cytochrome driven drug metabolism. Since then, other agents (tigracrelor AKA Brilinta, prasugrel AKA Effient) with a similar mechanism of action but more consistent metabolism have come on market,
An opinionated take on NEJM highlights for September 2019
Best care vs. good care In wealthy countries, the recommended standard of care can often lead to complex medication regimens requiring frequent follow-ups: this can be very challenging for people who though they live in wealthy countries but are poor themselves. In developing countries, efforts have been made to prioritize simplicity and population level impact through one-size fits all polypill interventions, but that has not been tested in the US. Here the authors report on a randomized study including 303 individuals living in poverty and at risk for cardiovascular disease.
Bolting a full-risk engine onto an urgent care chassis in New York
Last month, Warburg Pincus closed on previously announced plans to acquire a major multi-specialty practice in northern New Jersey (Summit) and combine it with an urgent care network centered in the New York metro area (CityMD). The deal reflects private equity’s recognition that, as the stand-alone urgent care business model is increasingly vulnerable, the valuations in accountable care are increasingly compelling. Urgent care’s evolution Early on, urgent care entrepreneurs focused on filling the gap between overscheduled primary care and expensive ERs. Ramp the visits per day high enough and the
Busy summer: An opinionated take on NEJM highlights for July/August 2019
Is the lack of new (non-viral) antibiotics a market failure? A lament about the lack of success in getting the biopharma industry to invest sustainably in the development of new antibiotics against highly-resistant organisms, and a recommendation “it is time to seriously consider the establishment of nonprofit organizations for developing these lifesavings drugs”. Let’s be clear; the reason economic viability of this therapeutic area is problematic is due to three confluent factors: (1) treatment is curative – i.e. does not provide recurrent revenues (2) the targeted population is small (3)
Choosing your customers wisely: are hospitals the right place to engineer the future of healthcare (and the software services to support it)?
MSFT’s pathbreaking alliances in healthcare services are impressive and well designed to grow adoption of their Azure cloud over the medium term. But if MSFT wants to be at the forefront of change and maintain a robust hold on healthcare cloud share in the long-term, their publicly disclosed partner set seems highly incomplete[1]. The two major alliances announced this year – Walgreens and Providence St. Joseph (PSJ) — are predictable outcomes of the emergence of the UNH, CVS/AET and CI/ESRX triumvirate. Healthcare’s anxious mid-tier services players need enablement partners with
Fishing for nucleic acids: An opinionated take on NEJM highlights for June 2019
Huntington’s disease: light at the end of the tunnel? The awful thing about Huntington’s is that in most cases, people know they are going progressively lose their mind at an early age, but there is absolutely nothing they can do about it. Recently there has been tremendous excitement around suppressing toxic huntingtin production in the brain by using antisense oligonucleotides (ASOs) administered intrathecally (i.e. in the cerebrospinal fluid through the spine). Two ASOs are in full blown clinical testing: HTTRx (Ionis and Roche) which does not discriminate between mutant and
Full-service vs. self-service: an emerging bifurcation in healthcare
A clinical vignette: the cases of Jane and Joe Imagine if you will two individuals both at age 50. Jane is a project manager whose recent health care has focused on managing menopausal symptoms, a knee injury sustained while skiing, and moderate episodic depression, with a medication list of one chronic medication, and one medication as needed. Joe is a bus driver whose recent health care has focused on managing Type II diabetes, hypertension, and low back pain, with a regimen of 4 chronic medications, and 2 medications as needed.
Facing new vertically integrated competitors, WellSpan and Capital Blue Cross prepare for a long siege
Summary The Capital Region of Pennsylvania is shifting in “real time” from traditionally separate plan vs. plan competition and provider vs. provider competition to integrated vertical plan/provider vs. plan/provider competition Vertically integrated competition can initiate both arms races in delivery system capacity and new product and care management strategies The two big independents – WellSpan and Capital Blue Cross – are trying to match the disruptors with their own capital spend and a vertical alliance Once you cede decisions on terrain and timing to the competitor, you must make do
An opinionated take on NEJM highlights for May 2019
TAVR for all? TAVR has become the standard of care for patients who need an aortic value replacement but are at high/medium surgical risk. But what about those at low-risk? Two studies answer that question, one with the Edwards device and the other with Medtronics. Both show that TAVR is superior along a number of end-points (stroke, hospitalization duration, atrial fibrillation) both at 30 days and at 1-2 year. Long-term outcomes remain a question though. Low-risk patients are younger (mean age 73-74) and will live with their valves longer, which
Amazon to startups: stay close to the consumer and let us own the platforms
Amazon’s healthcare play appears to be heavily focused on platforms rather than specific applications They would prefer startups focus on elements that are truly differentiating for consumers and let Amazon take care of the infrastructure Early-stage companies investing in their own back-end services may find their dollars wasted or their applications incompatible with Amazon The following insights around Amazon’s healthcare strategy rely on comments made by Eliot Menschik, Global Head, Healthcare + Life Science Startups, at Amazon Web Services and other speakers at the recent TiECon East conference. Because of
OptumCare’s legacy entanglements could slow its site-of-service shift
By bringing together accountable-minded physicians, urgent care and ambulatory surgery centers (ASCs) on a national scale, OptumCare could prevent a lot of avoidable hospital care and move much of what remains to lower cost sites of service. Wrap a capitation business model around it and you have a powerful “anti-system” – profitable for itself and toxic to hospital margins. OptumCare has a long way to go to put this theory into practice. It is still in only ~35 of its target 75 markets. And, within many of those 35 markets,
It’s in the brain: An opinionated take on NEJM highlights for April 2019
He’s dead, Jim As previously widely advertised, the BACE-1 inhibitor verubecestat (Merck) (and in journal correspondence atabecestat, Janssen) has now failed in a population with very early signs of cognitive impairment (this after a failure of those agents in mild-moderate Alzheimer’s). Target engagement clearly occurred with a decline of the amyloid detected through PET imaging in the treatment arms and an increase in the placebo arm. However, if anything, cognition declined more in the treatment arm than in the placebo arm after 2 years on study. A silver lining is
An opinionated take on NEJM highlights for March 2019
Target assessment with genetic polymorphisms Please bear with me for a long (but interesting!) story. Bempedoic acid (Esperion) is an inhibitor of ATP citrate lyase (ACLY), an enzyme in the cholesterol synthesis pathway (upstream of HMG-CoA reductase, the target of statins). In a study of 2,230 patients at high risk for cardiovascular events, on maximum statin therapy, and LDL > 70 (basically the PCSK9 target population), bempedoic acid was well tolerated and lowered the LDL by around 16% – a substantial effect. This would potentially position bempedoic acid, an oral
February was short and cold: An opinionated take on NEJM highlights for February 2019
Targeted conjugated cancer therapeutics – so few, but may be more soon The idea that one could combine the precision of a targeted biologic with the potency of a traditional cytotoxic to demolish a tumor has been around for decades, but with very rare exceptions, has not had the level of traction one would have expected. But this month, the journal has two studies reporting on these types of therapies, both in breast cancer. One shows that in a group of heavily pre-treated triple-negative breast cancer patients, sacituzumab govitecan-hziy (Immunomedics)
There’s always a bigger fish: healthcare services giants are looking anxiously over their shoulders
With the closing of the CVS/AET and CI/ESRX combinations, healthcare services are now led by a triumvirate of vertically-oriented goliaths. And we can anticipate that there will be more care delivery acquisitions and investments to fill out the new vertical platforms—just as the leader UnitedHealth Group (UNH) continues to invest in its care delivery arm (with the pending acquisition of DaVita’s physician group) a decade after it first went into the clinic business. The extent to which the two new combinations have allowed legacy constituents CVS, AET, CI and ESRX
Methods towards better care: An opinionated take on NEJM highlights for January 2019
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
On the uses of genetic information in disease: An opinionated take on NEJM highlights for December 2018
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
Eating your way out of disease: An opinionated take on NEJM highlights for November 2018
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
New class of therapeutics calls for new regulations: thoughts on the FDA’s new process for regulating digiceuticals
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
T-cells are everywhere: An opinionated take on NEJM highlights for October 2018
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
An opinionated take on NEJM highlights for September 2018
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
An opinionated take on NEJM highlights for August 2018
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
What’s harder, making new drugs or improving care delivery at scale? An opinionated take on NEJM highlights for July 2018
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