Author: Marc Herant

Recon takes an analytical look behind select developments in healthcare

We may figure out cancer before we figure out the healthcare system: an opinionated take on NEJM highlights for November 2016

“My name is T-Cell…, James T-Cell” Immune T-cells are licensed to kill other cells through a quick molecular kiss of death, and as such are potentially powerful allies in controlling a tumor. For obvious reasons this killing power is under strict regulatory control and in particular T-cells display PD-1 proteins on their surface, which when engaged by the ligand PD-L1 on another cell, protects that cell from being killed. Tumors often display high levels of PD-L1 so that disrupting the interaction between PD-L1 and PD-1 can enhance the effectiveness of

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An ad page in the NEJM and the future of cancer care

I am not sure how many docs continue to do this, but I still read the actual hard copy of my NEJM, and that means I flip past ad pages with smiling grandfathers playing with grandchildren thanks to supercalifragilistic products on my way to scholarly papers with tables and figures.  But this time, I stopped in puzzlement when I came across exhibit 1; Intermountain is a health system based in Utah, very highly respected for its sound approach to quality and cost control[1], but not broadly well known for cancer care

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An opinionated take on NEJM highlights for October 2016

Continued progress in multiple myeloma About 25,000 patients are diagnosed with multiple myeloma yearly in the US. Despite being initially treatable, typically this disease is ultimately lethal. Following a highly successful phase 1-2 study a monoclonal antibody against a marker of myeloma cells (daratumumab, Janssen) underwent phase 3 studies in combinations with established mainstays of therapy (the proteasome inhibitor bortezomib and the immune modulator lenalinomide) in a patient population several years out from their initial diagnosis.  Results were stellar, with the inclusion of daratumumab decreasing the disease progression rate by

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An opinionated take on NEJM highlights for September 2016

Taking a page from HIV to build a response to opioid abuse A couple of perspectives on the challenges of treating individuals who suffer from opioid dependence. The first highlights the importance of integrating medication assisted treatment (e.g. methadone or buprenorphine) into hospital and post-hospital care – plausibly an ED visit or a hospital stay for an event triggered by opioid abuse (such as an overdose) is a significant opportunity to go beyond treating the acute issue and starting patients on long term treatments. In the second, the author recalls

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An opinionated take on NEJM highlights for August 2016: cleanliness is not next to healthiness, testing before thinking, a long slog for precision medicine

There is such a thing as too much hygiene The prevalence of asthma in children has increased dramatically over the last few decades. Observational studies have shown that children in “dirty” environments such as farms seem to be relatively protected from asthma.  A theory is that the lack of exposure to microbes leads to higher sensitivity to allergens, but this causality has been hard to show. Amish and Hutterite farm communities are genetically similar, but Amish rely on animals instead of machinery, and Amish children have much lower incidence of

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NEJM Highlights for July 2016: Bayesians vs. frequentists, PCPs vs. specialists, SGLT-2 vs. GFR

Adaptive clinical trials slowly coming of age In an adaptive clinical trial, the protocol of the trial is allowed to change in a pre-specified manner during the study based on on-going study events.  In this issue of the NEJM, two research papers, one perspective, and one editorial are devoted to the I-SPY 2 trials which dynamically changed randomization procedures for neo-adjuvant (pre-surgery) chemotherapy for stage II and III breast cancer and allowed accelerated identification of subgroups that benefit from a novel tyrosine kinase inhibitor (neratinib – Puma Biotechnology) and a

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NEJM Highlights for June 2016: Improving care delivery is just plain #%^*! hard

Disappointing interim results from two ACA experiments Two papers reporting results from ACA experiments – the Comprehensive Primary Care (CPC) Initiative in which primary practices were incentivized with fairly generous payments to strengthen care management activities such as management of chronic conditions, or coordination of care – and the ACO initiatives (2012 cohort) described elsewhere in many reviews. Both papers provide a view on the early impact of these initiatives (2 years out) on costs and outcomes by using well controlled no-intervention comparison groups. The upshot is that so far,

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The many ways in which decreasing volatility in individual health care utilization is valuable

It is a long-standing hypothesis shared by many providers that community-based interventions that improve primary care could lead to overall healthcare savings by preventing (or delaying) the occurrence of medically expensive conditions.  Rigorously proving this has been difficult, and only a few appropriately controlled studies have been published. In a Letter to the Editor of the American Journal of Managed Care[1], my colleague Alex Brown and I commented on an earlier article[2] evaluating the impact of a community health worker (CHW) intervention on healthcare costs. The study showed no significant

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NEJM Highlights for May 2016: Referral for surgery, and a miscellany of interesting biochemistry

Surgical volume and referral for surgery: The impact of surgical volume on outcomes has been well documented, but is it top of mind with physicians referring patients to surgery? Readers of the Journal were polled on a hypothetical scenario whereby a community physician would be referring a patient in need of a major surgical procedure to either a nearby community hospital with a well-respected general surgeon doing approximately 5 of these cases a year versus a tertiary medical center 40 miles away. The great majority of readers chose the option

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NEJM Highlights April 2016: Value and values: RBRVS, ACA and readmissions, E-cigs

RBRVS: an acronym we ought to think more about RBRVS stands for the Resource Based Relative Value Scale, and codifies the time and effort involved for a comprehensive set of physician activities on which Medicare payments are based. In this perspective, the authors highlight that most value-based payment (VBP) systems currently under development are essentially built as modifiers on top of the RBRVS. But the RBRVS has two major issues with it: it is “downward sticky” and has not evolved to take into account increased efficiency (e.g. automation), and it

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NEJM Highlights March 2016: Getting value for money in healthcare, Zika bad news, linking the microbiome to the metabolic syndrome

Could Uber happen to healthcare? A Perspective article that points out that the success of Uber is rooted in the flaws of an industry where customer convenience and value for money took the backseat to the interest of a set of service providers highly protected by regulation. Sounds familiar?  Obviously, the regulatory moats of healthcare are much wider and deeper, but in a curious mix of warning (watch out!) and encouragement (this will be good for you if you embrace it!) the authors argue that the medical profession should not

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NEJM Highlights Feb 2016: metrics for all, ROI perversion, less memory loss, the value of a kinder gentler residency

Defining success in health care A perspective advertising yeoman’s work of the International Consortium for Health Outcomes Measurement (ICHOM) which has defined specific metrics for dozens of diseases for which there are no widely accepted standards defined so far. If followed broadly, this will greatly facilitate performance comparisons across systems, improvement of processes of care delivery, and the implementation of value based contracting. Standardizing Patient Outcomes Measurement (free access)   Public health gets no respect A lament on how population health interventions tend to be beholden to positive ROI standards

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NEJM Highlights January 2016: a medley of social service, OB, data mining, obesity, and ESRD

Leveraging community services for health In poor individuals, a lot of health issues are intimately connected to their socioeconomic circumstances. However, at the system level, there has been a chronic lack of integration between social and health services. Several efforts have tried to remedy this, notably through integration of the Medicare and Medicaid components for duals in the financial alignment demonstration projects sponsored by CMS. But a there are a lot of social services that are not part of Medicaid; and recognizing the need to ensure awareness, and access, CMS

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NEJM Highlights December 2015: providing effective healthcare is hard and expensive – but ineffective care can be even more expensive – and defining what expensive means in healthcare is hard

A new focus on the diagnostic reliability of clinicians Two perspectives highlighting the recent report from the National Academy of Medicine (formerly IOM) entitled “Improving Diagnosis in Health Care”.  Diagnostic error has long been the invisible side of poor medicine compared to medication errors, or a towel forgotten inside the patient and the like.  But the growth of health IT is both exposing diagnostic error and bearing the seeds of a solution, initially through rule-based automated checks and reminders, but likely eventually through a much more guideline driven practice of

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NEJM Highlights November 2015: systems biology, RSV progress, a first in diabetes, hypertension goals, the case of Maryland

Systems biology finally gets real: an unexpected use for a diabetes drug Chronic Myelogenous Leukemia (CML) has been the poster child first for a disease with a precise genetic cause (the Philadelphia chromosome), and then for targeted drug design (with imatinib – Gleevec). Unfortunately, few patients achieve a complete response to therapy which means that they have to stay on drug indefinitely. This commentary highlights recent research which shows that pioglitazone (Actos), an approved diabetes drug that activates a specific cellular pathway (STAT5) can synergistically enhance treatment with Gleevec to

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NEJM Highlights October 2015: what to do, how to do it, and to whom

What are annual physicals for? Annual physicals are costly (~$10 billion annually) and have never been shown to improve outcomes, but people value them. In this dichotomy lies a lot of the inner tensions of medical care: between delivery of technical care, and nurturing of human relationships, and those are illuminated by two articles in counterpoint.  In the end though both sides come to a point of view that is not altogether dissimilar – that what is needed is not an annual physical, but some sort of preventive care/health review

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Working paper: the coming age of algorithmic medicine

Summary In this working paper, we develop the following thesis. In the not so distant future (a decade or two), medicine will be largely governed by algorithms — highly deterministic clinical pathways characterized by a high level of reproducibility of care — that will be developed and improved by providers. These algorithms will include individual patient preference branch-points but not individual provider preference.  As a result, payers and providers will agree on coverage on the basis of a set of algorithms and a process of how they should evolve; providers

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NEJM Highlights September 2015: cells, cells, cells

Promise for systemic amyloidosis (and beyond?) Systemic amyloidosis is an uncommon disease in which abnormal cells (typically antibody-producing B cells) produce large amounts of protein that deposit as amyloid fibrils in various organs (heart, kidney, liver). These are the same kind of deposits that create plaque in the brain in Alzheimer’s disease.  In systemic amyloidosis, the deposits cause organ damage, failure, and death and treatment options are limited.  GSK is developing a monoclonal antibody directed at serum amyloid P (SAP), a naturally occurring glycoprotein that binds to amyloid fibrils. The

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NEJM Highlights August 2015: cancer and joints

The emergence of a new approach to drug development in cancer Cancers are classified by the organ or tissue from which they arise, but as our molecular understanding increases, another level of categorization is emerging based on the molecular characteristics of the tumor. In a novel but sure to be growing approach, Roche/Genentech tested their drug vemurafenib (Zelboraf, currently approved for melanomas with the BRAF V600 mutation) in a study population that was largely agnostic to tumor provenance as long as it was BRAF V600 positive. 122 patients were enrolled

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NEJM Highlights July 2015: a first in class drug for cancer, Sovaldi cures renal failure too (sometimes), convenient primary care

Palbociclib – first to target cyclin dependent kinases – breast cancer As all biology majors know, cyclin dependent kinases are critical elements controlling the machinery of cell proliferation.  They have proved difficult targets due to their ubiquitous activity in both normal and abnormal tissue – until now. In a phase 3 study, about 500 patients with metastatic hormone positive, Her2 negative breast cancer were treated with palbociclib (Ibrance, Pfizer, recently FDA approved) vs. placebo.  The median disease progression time for patients on drug was 5 months longer than for placebo

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