“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 immune killing of tumor cells. Amplifying results from last year… Read More
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 in the way of centers like Dana Farber… Read More
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 half at 1 year. Daratumumab, Lenalidomide, and Dexamethasone… Read More
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 the tremendous progress in treating HIV/AIDS in the early 90s… Read More
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 asthma. In a fascinating study comparing Amish and Hutterite, it… Read More
Summary Cheap home devices are starting to generate a flood of high frequency, low latency biometric data, much of it of uncertain clinical value This uncertainty makes designing the service model difficult: high value use cases may get bundled with broader, low value, more speculative ones (e.g. behavior change), reducing overall ROI and uptake Given the patient-generated nature of the data and uncertain accuracy / calibration of the devices, use cases will need specific targeting or depend on subsequent clinical grade investigation to sort signal from noise High value use cases are likely going to require tightly designed delivery models… Read More
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… Read More
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, the CPC and ACO (v. 2012) initiatives do not show… Read More
Summary Livongo is marrying a cellular-enabled glucometer and a data cloud with patient engagement services to help manage sugar levels Glucometer incumbents could match Livongo’s technology but will struggle to counter the business model innovation By expanding into services, however, Livongo is expanding its potential competitive set to include incumbent downstream care providers If Livongo’s model demonstrates compelling value, both device and services incumbents could find ways to stitch together competing solutions in collaborative ecosystems Closed loops are great ways to develop value propositions but can be rickety for trying to scale a solution in healthcare given the frictions which… Read More
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 reduction in average cost… Read More