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 PARP inhibitor (veliparib – Abbvie).  Adaptive trials are described in an excellent review in the same issue – there are two salient points for this approach: (1) the need for a relatively quick individual outcome read-out compared to the overall length of the trial; (2) the requirement to do an enormous amount of thinking and modeling up-front mapping all the contingencies that could affect the studies.  But while the approach has been largely focused on drug development (that’s where the money is!), it really could have a tremendous impact on health delivery-focused pragmatic trials implemented through a flexible platform in a large health system.  I-SPY 2 — A Glimpse of the Future of Phase 2 Drug Development?; Adaptive Randomization of Neratinib in Early Breast Cancer; Adaptive Randomization of Veliparib–Carboplatin Treatment in Breast Cancer; Adaptive Designs for Clinical Trials; I-SPY 2 — Toward More Rapid Progress in Breast Cancer Treatment (subscriber access)


Winners and losers in bending the cost curve

An incisive perspective that squarely puts its fingers on upcoming pain points of the ACO program in particular, and the overall objective of controlling health care spending.  Given quality and patient satisfaction objectives, where is the lion’s share of the addressable costs? – They plainly lie with specialist and hospital utilization. And where is the locus of patient management most effective to reduce this utilization? – In primary care.  You can connect the dots… The Coming Battle over Shared Savings — Primary Care Physicians versus Specialists (subscriber access)


Slowing renal disease in diabetes

A frequent outcome of long-term diabetes is a decline of renal function that can eventually lead to kidney failure – in fact nowadays, about half the patients on dialysis in the US got there because of diabetes.  Empaglifozin (Jardiance, Lilly and BI) belongs to a relatively new class of agents that lowers blood glucose by blocking SGLT-2 (sodium/glucose co-transporter 2) in the kidneys and allowing glucose to be excreted in urine. In a 3 year randomized controlled trial involving more than 6,000 diabetic patients, the rate of worsening of renal function was decreased by a factor of 2.  This could have a significant impact on the rate at which diabetic patients end up on dialysis (currently, around 30,000 new US patients every year).    Empagliflozin and Progression of Kidney Disease in Type 2 Diabetes (subscriber access)



The New England Journal of Medicine is a premier weekly medical journal covering many topics of interest to the health sector. In this monthly series we offer a brief overview of highlights that might be of interest to our clients and others.

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