Last month, the NIA announced a $53M/5 year research collaboratory called IMPACT, to facilitate non-drug care improvements in Alzheimer’s and related dementias (ADRD) . Their document displays an impressive structure already, with ten core teams, led by many distinguished folks. They will “build capacity” in a resource that researchers can use to test “real world” ideas, perhaps exploiting data systems from health care institutions, based on the NIH Collaboratory model of pragmatic clinical trials (PCT). AlzGadfly wishes the new group well, and considers the arena important, but wants to know: who exactly benefits, in what timeframe?
So what’s a PCT? From the NIH online textbook: “Califf and Sugarman (2015) propose the following ‘common sense’ definition for a PCT when conducted in a healthcare context: [A trial that is] designed for the primary purpose of informing decision-makers regarding the comparative balance of benefits, burdens and risks of a biomedical or behavioral health intervention at the individual or population level.” So, the conclusions of a PCT might affect a care policy.
Got that? PCTs are different from randomized controlled trials (RCTs), set up to test whether one therapy is better than an alternative (placebo, or proven therapy), usually at the individual outcome level. So, the conclusions of an RCT might introduce a new therapy. [AlzGadfly is not gonna address the recent news of a company reassessing its outcome data of a certain amyloid monoclonal RCT…].
How are PCTs different from everyday Quality Improvement (QI) activities? Well, PCTs seem like a niche between RCTs and QI work, with some overlap, so the online textbook tackles that by providing a chart. AlzGadfly won’t pretend to really understands all the subtleties, but looking at a recently published infection control collaboratory study helps one see how things might work.
The NIH Collaboratory ABATE study, by Huang et al, studied whether certain hospital bathing techniques could prevent specific infections in non-ICU patients. Using “embedded” patients and the medical records in a healthcare system, over 50 hospitals were “cluster randomized” to using a technique or not, and they studied over 300,000 patient episodes. There was an IRB-approved waiver of consent. They found that chlorhexidine + nasal mupirocin didn’t really help, except in a post-hoc analysis of patients with medical devices like central lines (confounding oncology unit data is discussed). The authors and editorial point out some “real world” issues and limitations of the study, including caveats about interpreting the post-hoc analysis.
Infection control improvements are usually considered QI work, but ABATE was obviously massive “next level stuff,” especially in episode data. Interestingly, the participating healthcare system’s decision-makers made a real world choice to use the study as a springboard to change some infection control protocols.
One can imagine how a creative dementia researcher, with care improvement of institutionalized patients as a goal, might relish the opportunities of such a framework, especially the waiver of consent (one of the ten core teams is regulation and ethics). It does bring to mind whether the old QI Plan-Do-Study-Act cycle just needs to be applied more aggressively in AD care and/or how it might overlap “implementation science“, as used in cancer control parlance at the NCI.
A PCT might test active interventions, maybe a step up from “natural experiment” observational studies, which are nevertheless informative. Wattmo et al in Sweden, in a series of studies, has examined the association of ADRD drug usage and time to nursing home admission or mortality in a longitudinal cohort. Scherrer et al looked at metformin prescribing and the incidence of ADRD in a VA + HMO study. Lourida et al looked at over 190,000 in the UK with genetic and lifestyle data (choose to be healthy and maybe you’ll stay healthy if your genes allow it).
The term “collaboratory” is more than just a pleasant portmanteau. Coined by computer scientist William Wulf about 30 years ago, it’s basically a research concept made possible by the internet, with work done by different groups in different locations, sharing information. As used by the NIH, the term seems to have an emphasis on PCTs and population health. Let’s hope the results of this work will extend beyond “decision-makers,” with their “comparative balance” responsibility, to create tangible improvements in the lives of patients. If small numbers of subjects is a limitation of many care intervention studies, PCTs might help.
So, the NIA IMPACT Collaboratory will be a national resource for ADRD PCTs, like a consulting firm, one supposes. Here’s a crazy idea: let’s design a “Flashmob” effect for this expert group: you know, one of those social media contrivances when a group of folks milling about suddenly break out into a synchronized dance. Thinking about how to utilize existing patient cohorts and their medical records, coupled with clinical trial designers, biostatisticians and ethicists, one dreams that they could suddenly synchronize that precious expertise, and create a structure to massively accrue subjects for disease-modifying RCTs, and accelerate finding therapy that works. Cue the music!