Posted on 04/09/2020 9:26:32 PM PDT by SeekAndFind
UPMC announced Thursday that they are launching a new fast-track clinical trial for COVID-19 drugs.
The clinical trial developed by researchers at the University of Pittsburgh School of Medicine launched officials say addresses one of the most important debates during the COVID-19 pandemic: How should doctors decide between quickly adopting new therapies, such as the anti-malarial drug hydroxychloroquine, and waiting until they are tested in longer clinical trials?
“The solution is to find an optimal tradeoff between doing something now, such as prescribing a drug off-label, or waiting until traditional clinical trials are complete,” said Derek Angus, M.D., M.P.H., professor and chair of Pitt’s Department of Critical Care Medicine. “We’ve developed a way to do that with an adaptive clinical trial model that relies on a type of artificial intelligence known as reinforcement learning to identify the best, evidence-backed therapy for COVID-19 much faster than using the traditional scientific approach.”
Before COVID-19 emerged, Angus and a wide range of international collaborators had developed a platform, called REMAP-Community Acquired Pneumonia (REMAP-CAP), designed to find optimal treatments for severe pneumonia both in non-pandemic and pandemic settings. When COVID-19 began circulating, REMAP-CAP was rapidly adapted, as per its intent, to incorporate additional treatment regimens specifically targeting the SARS-CoV-2 virus. The international team describes the REMAP-CAP platform in a manuscript published today in the Annals of the American Thoracic Society (AnnalsATS).
REMAP (randomized, embedded, multi-factorial, adaptive platform) allows researchers to rapidly test multiple treatment approaches simultaneously at a lower cost and with fewer patients than traditional clinical trials. The REMAP design, first described by Angus in 2015 in the Journal of the American Medical Association (JAMA), is a flexible version of what are called “adaptive platform trials.” “Adaptive platform trials are rapidly being endorsed by the U.S. Food and Drug Administration, the Bill & Melinda Gates Foundation and others as a long-needed revolution in clinical trials,” said Angus, who holds the Mitchell P. Fink Endowed Chair at Pitt.
He compares the REMAP approach to a chef offering a prix fixe menu with appetizer, main course and dessert. The chef may try various combinations, serving sizes and options, sometimes leaving out the appetizer or dessert, and adjusting on the fly as plates come back scraped clean or barely touched, until hitting on the combination that sells best.
The UPMC-REMAP-COVID19 trial, built on the backbone of the REMAP-CAP platform, will be particularly powerful because it is being integrated with the electronic health record system at UPMC, noted Angus. “In a pandemic, doctors will not have the time to debate the pros and cons of every possible clinical trial. By building this one-stop solution at the point-of-care, we are rolling out an approach that can assure that every patient admitted with COVID-19, if they choose to, can be enrolled in the program.”
“We must throw out old ways of thinking and fuse clinical care and clinical research into one extremely efficient system,” said Angus, who authored a recent viewpoint in JAMA advocating for the “learning while doing” approach. “This is an unprecedented pandemic and we need an unprecedented response.”
UPMC-REMAP-COVID19 will open across UPMC’s 40-hospital system and begin with multiple treatments tested simultaneously in different combinations — including hydroxychloroquine, steroids and medications called immunomodulators that alter the responsiveness of the immune system. If new drugs need to be tested, they are simply rolled into the platform as study amendments, rather than tested in separate free-standing trials. All participants will receive the current standard of care, and most also will receive one, two or three of the experimental treatment options. This means that, at launch, only 12.5% of participants will be strictly assigned to the placebo arm of the trial and, within weeks, researchers expect that about 99% of patients will be receiving one or more active therapies specifically targeting COVID-19.
Furthermore, because the UPMC-REMAP-COVID19 platform is connected to the worldwide REMAP-CAP, the trial learns from the entire international experience. REMAP-CAP is enrolling patients with COVID-19 in North America, Europe, Australia and New Zealand, and expanding rapidly.
“The trial design uses a machine-learning model that incorporates data from patients enrolled across the world to continuously learn which therapies and combinations of therapies are performing best,” explained AnnalsATS co-author Scott Berry, Ph.D., president and senior statistical scientist of Berry Consultants, who worked with Angus and his colleagues to build the statistical model. “Last week, the Chief Medical Officer of the United Kingdom’s National Health Service urged every hospital in the country to participate in this trial. As more institutions join, the model learns faster.”
If one of the treatments shows early signs of performing better than the others, patients are automatically enrolled more often into that treatment option. Physicians can be assured that they are always betting on the winning horse in the moment, and poorly performing options are quickly discontinued.
“This allows us to always rapidly identify which treatment works best, while keeping the number of patients needed to achieve statistical significance low,” said Angus. “It also means we get the best treatment to the most patients right out of the gate.”
[[“The solution is to find an optimal tradeoff between doing something now, such as prescribing a drug off-label, or waiting until traditional clinical trials are complete,”]]
There is NO trade off- you go to war with the army you have at hand- not some future army that will only be able to swoop in when the world lays reeling from the year’s long carnage—
It is stunning that this is even a question- IF we find it does no good whatsoever, then we gave it our best shot with the army we had on hand- but all indications show a strong likelihood that it is working- and working marvelously-
Debating this any further is just irresponsible and immoral at this point- use what you have now, WHILE working on further treatments if you feel you must- in the meantime, 10’s of 1000’s will benefit from the drugs that are proving to be so helpful now!-
this looks really good and SOUNDS like results will develop in real-time instead of the fake studies NIH and FDA are sponsoring that won’t have results until July or August or even six months from now ...
still, with a 12.5% chance of being in the placebo group, i would refuse to be part of the study and demand the hydroxychloroquine/zith/zinc treatment ...
plus, i still don’t see how it’s even ethical to HAVE a placebo group for a study of a treatment being successfully used worldwide ...
Thousands will die while these arrogant jerks jack around.
Exactly. Seems to me like a lot of lawsuits could be coming. Gov. Cuomo should be sued.
This is brilliant.
If you know a fair amount about formal, multivariate designed experiments, the sample sizes and sheer amounts of tests needed can be staggering. Taguci came up with methods long ago, to vastly decrease the number of trials, but required each branch to be orthogonal.
Combining it with adaptive AI to adjust each branch on the fly is genious. It should work spectacularly. If the FDA is onboard, and it sounds like they are, we’ll have optimal treatments, very likely using HCQ, perfected and endorsed by the feds.
Trump wins again. MSM will be suicidal. “Trump Cure Works!” will be headlines.
It can no longer be denied that the entire medical community is trying to stop the deployment of what we know will work.
It is deliberate. The socialist doctors of America and their medical organizations are doing everything they can to destroy the nation with their lies. They lied about the impact of this virus. They lied about what would work in treatments. They lied about the motivation of the good doctors who have actually put people back on their feet. They lie about Donald Trump being wrong when he is dead nuts on right in every aspect.
They are nothing but feel good murderers and liars who have manipulated their whole lives to get into positions of power and influence only to introduce us to socialized death squads walking in lock step after doctor ezekiel.
“...plus, i still don’t see how it’s even ethical to HAVE a placebo group for a study of a treatment being successfully used worldwide ...”
Exactly! The FDA is loathe worldwide for insisting on these long, drawn out double blind studies, and if no comparable treatment exists, using a placebo. Worldwide, Physicians know and hate the ethics.
When likely outcomes are death or serious injury, telling patients that they might get the placebo, well, I truly feel bad for all involved. Except the friken FDA.
It’s why although most new drugs and med devices are developed in the USA, first clinical trials are often done in Europe or Brazil, etc. There, the rules are different. Individual med centers—hospitals—can sponsor studies, with saner placebo use. Smaller sample sizes, too.
Well known issue. Awful.
UPMC is my HMO. Pitt is my school.
Hail to Pitt!
By the time they develop and initialize this “fast track” and then diagnose the AI algorithms when they screw up, 1000s of people will have gotten better by simply saying Yes Doc, gimme HCQ.
It would appear that in late March of 2020 a builder from Queens knew more than the entire global medical establishment combined.
Disclaimer: Opinions posted on Free Republic are those of the individual posters and do not necessarily represent the opinion of Free Republic or its management. All materials posted herein are protected by copyright law and the exemption for fair use of copyrighted works.