NEJM Archives - Recon Strategy

Two steps forward, one step back: an opinionated take on NEJM highlights for January 2018

Marc Herant January 29, 2018

Playing chess against cancer Tumors are not intelligent, but, because they have escaped mutational control, they constantly probe for mutations that will allow them to escape chemotherapeutic suppression. The epidermal growth factor receptor (EGFR) is a frequent driver of malignancy in the lung and as such, a target for EGFR inhibitors such as erlotinib (Tarceva, Roche) or gefitinib (Iressa, Astra Zeneca); unfortunately, tumors initially responsive to these agents quickly develop mutations which make them resistant. Osimertinib (Tagrisso, Astra Zeneca) was designed to overcome the most common resistance mutations and has

A golden age for gene therapy: an opinionated take on NEJM highlights for December 2017

Marc Herant January 1, 2018

Successes in gene therapy for hemophilia B and A Hemophilia A and B are X-linked genetic diseases which prevents the formation of functional coagulant factors VII and IX respectively and cause a propensity to bleeding in about 20,000 people in just the US. The standard of care of intravenous administration of recombinant factors is effective but also burdensome, expensive, and does not fully prevent the disabling sequellae of the disease caused by repeated bleeding in the joints. A possible cure is to deliver a functional copy of the defective gene

Between the very common and the very rare – An opinionated take on NEJM highlights for October 2017

Marc Herant October 30, 2017

Between the very common and the very rare – An opinionated take on NEJM highlights for October 2017 Another tool for prevention in cardiovascular disease Taking aspirin daily has been standard of care for cardiovascular disease for decades, but attempts to demonstrate the additive usefulness of other agents to prevent clot formation have not been successful. Now things have changed: in a large study of patients with established cardiovascular disease, those who took rivaroxaban (Xarelto, Bayer) daily on top of aspirin did markedly better than with aspirin alone, although

A strong close to a banner year for progress against cancer: an opinionated take on NEJM highlights for December 2016

Marc Herant January 5, 2017

Successful use of CAR-T therapy in a solid tumor Chimeric Antigen Reception T-cells (CAR-T) are immune cells molecularly engineered to seek out and destroy cancer cells; the push to develop them into a scalable generally usable treatment is likely the most exciting challenge in cancer right now. Successful CAR-T use has so far been generally confined to hematological tumors. In a brief report, a group from City of Hope reports on the use of CAR-T in a patient who was dying from an advanced, aggressive form of brain cancer, which

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

Marc Herant December 1, 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

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

Marc Herant November 13, 2016

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

An opinionated take on NEJM highlights for October 2016

Marc Herant November 2, 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

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

Marc Herant September 2, 2016

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

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

Marc Herant August 2, 2016

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

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

Marc Herant April 3, 2016

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

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

Marc Herant February 29, 2016

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

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

Marc Herant January 5, 2016

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

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

Marc Herant November 2, 2015

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

NEJM Highlights September 2015: cells, cells, cells

Marc Herant September 29, 2015

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

NEJM Highlights August 2015: cancer and joints

Marc Herant September 1, 2015

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

NEJM Highlights May 2015: a read on ACO performance, progress in cystic fibrosis treatment, yes developing new drugs is expensive, rethinking industry-medicine relationships, CVS Caremark and smoking cessation

Marc Herant May 29, 2015

Early results of the ACO experiment: directionally right, but impact is still small In this study, the authors compare metrics for Medicare beneficiaries assigned to the 32 ACOs part of the Pioneer program vs. matched beneficiaries who were not in an ACO. With respect to costs, they find that compared to contemporaneous trends observed in non-ACO members, the ACO beneficiaries yearly spending was approximately $100 below trend (a 1% savings). In a hint of a reversal of a secular trend in health care, office spending visit expenditure increased more in

NEJM Highlights April 2015

Marc Herant May 1, 2015

The rise, fall, and rebirth of the Chinese healthcare system A fascinating account of the evolution of the Chinese healthcare system which almost seems to be an upside-down picture of the rest of the country’s development. Tremendous public health improvements occurred in the 50s, 60s, and 70s but the transition to a free market model of healthcare in the 80s seems to have been a disaster only mitigated by the general increase in wealth of the population. Seeing this as a major threat to social stability, the Chinese government has been

NEJM Highlights March 2015: Progress against Crohn’s, PCSK9 inhibitors coming through, comparative effectiveness for diabetic macular edema, Eric Lander encourages the FDA on genomic testing regulation

Marc Herant April 1, 2015

A promising agent for Crohn’s Disease, a miserable illness Crohn’s is an inflammatory bowel disease that is notoriously unpredictable; flares can affect any part of the digestive tract and lead to grave complications. In this double-blind phase 2 study, patients were dosed with mongersen (licensed by Celgene) an anti-sense oligonucleotide that down-regulates the expression of a protein implicated in the inflammatory cascade. In general these classes of medications have to be given parenterally but in this case the target is the gut so it can be taken orally. At two weeks

NEJM Highlights February 2015: the most boring month in my NEJM reading memory

Marc Herant March 2, 2015

Our selection from a month with relatively few exciting articles – perhaps this long Boston winter has us all down. Precious metals and health plan buying: The implementation of the ACA has placed new decision making on individuals purchasing health insurance on the exchanges. In this report, the authors argue based on experiments that for many individuals, reversing the gold-silver-bronze nomenclature (gold becomes bronze and vice versa) reverses the preference independently of the underlying characteristics of the plans. For the public health advocate this highlights the need for educating shoppers, and

NEJM Highlights January 2015: Dengue vaccine, Informed consent, Cancer drugs and Tiering for selection

Marc Herant February 5, 2015

A vaccine for dengue finally nears the market Dengue is a mosquito transmitted viral infection that is often severe and occasionally fatal, and that has been identified as a growing public health threat, largely in the developing world but also with inroads in developed countries with hundreds of millions of cases yearly world-wide. At this time, there is no vaccine or treatment for dengue other than supportive care. In a placebo-controlled study, a dengue vaccine from Sanofi-Pasteur covering all 4 serotypes of dengue was found to be 60% efficacious in preventing

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Recon takes an analytical look behind select developments in healthcare