New effort aims to speed up clinical trials for common diseases


A A group of scientists who have done perhaps more than any other to test new treatments for Covid, including establishing that the steroid dexamethasone can save lives, are now focusing on the rest of medicine.

First step announced today: a partnership with the Parisian drug giant Sanofi.

Sanofi will grant Protas, a British non-profit organization, $6.8 million to begin work to make clinical trials faster and much cheaper. It aims to build on what researchers have learned studying treatments for Covid-19 to test drugs for heart disease, cancer, depression, Alzheimer’s and other common conditions.


“You really have to think about how to get better evidence at lower cost to have a better impact on public health,” said Sir Martin Landray, CEO of Protas and Professor of Medicine and Epidemiology at the University of Oxford. “And that’s the motive.”

Landray is known for helping lead an effort that did more to find drugs to treat Covid than perhaps any other. The study he co-led, RECOVERY, used a network of UK hospitals to find out if a range of potential treatments helped hospitalized Covid patients. The study showed that hydroxychloroquine, convalescent plasma, and the anti-HIV drugs lopinivir and ritonavir were ineffective for these patients. But he found that dexamethasone, the monoclonal antibody cocktail REGN-Cov and the rheumatoid arthritis drug Actemra all helped hospitalized Covid patients survive.


This was all the more impressive considering how many other efforts to definitively test potential Covid drugs have failed because the studies were too small or disorganized, and because they simply took too long to complete. to start up. RECOVERY delivered results before a large clinical trial of hydroxychloroquine planned by Swiss pharmaceutical giant Novartis could even start. Plus, it was a lot cheaper than research studies usually are.

It is not uncommon for pharmaceutical companies to spend hundreds of millions or even billions of dollars to conduct a single clinical trial. The RECOVERY effort, Landry said, cost less than $10 million.

Now, he told STAT in an interview, it’s time to apply the lessons of this effort to other drugs.

“If trials continue to cost $1 billion or $2 billion each, we won’t get many new treatments for common diseases,” Landray said. “And that’s not good value for patients and it’s not good value for those who pay for their care or provide their care.”

In a statement, Dietmar Berger, chief medical officer of Sanofi, said the company was “delighted” to work with Protas.

“With this collaboration, we are taking a bold step to significantly reduce the cost of some of our clinical trials, focusing on what matters most to patients, physicians, regulators and payers,” Berger said.

The idea behind Protas before the pandemic. In February 2020, Landray co-authored an article in the New England Journal of Medicine that denounced the “real world evidence” that many pharmaceutical companies were increasingly relying on as a “myth,” while praising the randomization, the most rigorous hallmark. medical studies, such as “magic”.

“Real-world evidence” is often used as another word for what are traditionally called observational studies or databases, in which researchers follow large numbers of people in order to try to tease out the benefits and risks of medical treatments. But they are considered weaker than studies known as randomized controlled trials – in which patients are randomly assigned to receive either a new treatment or the best possible care that is otherwise available.

These trials work because selecting patients essentially by coin toss yields not only an answer that takes into account what the researchers know that might influence an outcome, but what they don’t know. This has been the standard in medicine since shortly after World War II, when British researchers proved the antibiotic streptomycin to be effective in treating heart infections. Traditionally, the United States Food and Drug Administration considers two randomized controlled trials the best evidence that a drug works.

But randomized trials have a problem: they are difficult to carry out and are expensive. And spending has increased dramatically over the past few decades.

For example, studies of heart medications have regularly approached or exceeded the billion dollar mark. In the early 2000s, Pfizer said it was spending nearly that amount to study a drug to boost good cholesterol. (In a huge disappointment for the company, this drug increased the death rate in a large clinical trial.) More recently, two new cholesterol drugs called PCSK9 inhibitors, one from Amgen and the other from Regeneron and Sanofi generated huge drug bills. businesses and ended up generating few sales.

This means, Landray said, that heads of pharmaceutical research trying to decide which products to develop are looking at drugs for heart disease or Alzheimer’s disease and seeing not only a slim chance of success, but an incredibly costly roadblock to success. end of the process. Additionally, drugs for rare diseases, including subsets of cancers, can often be made in much smaller and less expensive studies. But because these drugs are expensive, they can be just as lucrative.

This, in turn, creates a situation where pharmaceutical companies, instead of trying to study drugs in as many people as possible, try to limit their studies to the group they think is most likely to show benefit. .

Landray jokes that it’s as if the message from companies funding studies is often: “Dear statistician, can you provide us with a mathematical justification for limiting the scope of this study?”

But there is a potential solution: what is called a large single trial. Part of the reason clinical trials are so expensive is that they are often conducted by companies known as clinical research organizations who charge per patient. Another is that more and more processes, such as additional blood tests, measurements and follow-up visits, are being added. This gives more information, but also increases the cost.

Landry advocates a different strategy: remove as many costs and processes as possible to make the trial easier to conduct. For example, a study trying to figure out whether prescribing a drug to someone lowers their risk of dying need only ensure that they find out if they die. In this extreme case, many other data collections can be skipped. By simplifying the execution of the trial for frontline doctors and nurses, it becomes easier to recruit patients from hospitals where top academics rarely visit, meaning data is collected from a more diverse population – geographically, socio-economically and in terms of race and ethnicity.

This is the approach that was tested in RECOVERY. This was not the first time the simple approach was used. Eric Topol and Robert Califf, who is currently considered the next head of the FDA, used this strategy in a study of a clot-busting drug a quarter of a century ago. And Landry and his colleagues have used the approach in studies of heart drugs, including a Merck reformulation of the B vitamin niacin. At the time, niacin was commonly used as a heart medication, and Merck thought its version would be less likely to cause facial flushing. Instead, Landry and his colleagues found that the drug had little effect but increased the risk of severe bleeding and infection in patients. A similar strategy has cut costs for testing Novartis’ new cholesterol-lowering drug, Leqvio, which is currently being rolled out by the National Health Service as part of a program that will aim to monitor its effectiveness.

The desire to replicate this model is what led to the creation of Protas as a non-profit association. (The world, Landray said, didn’t need another for-profit clinical trials company.) But there’s still a long way to go. Sanofi’s money is just a drop in the ocean when it comes to pharmaceutical company spending. Landray will need more big partners. And he says he will spend the next few years building the infrastructure the nonprofit will need.

But it’s a start.


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