Home Brussels How the pandemic is causing a rethink in the way we study drugs

How the pandemic is causing a rethink in the way we study drugs

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This article is the product of a POLITICO Working Group.

When the news broke in January that the Oxford/AstraZeneca coronavirus vaccine hadn’t been fully tested on over-65-year-olds, it confounded health authorities and made what was already a complicated vaccine rollout in Europe even choppier. 

Despite a green light from the European Medicines Agency, which approved the shot for all ages, country after country decided to take a cautious approach, restricting the rollout to younger groups — for whom plenty of evidence had been collected. 

In the end, however, there were no efficacy problems — and AstraZeneca was vindicated. But it took a Scottish study published well after the vaccine was approved to put doubts to rest. Those findings helped reverse the tide of skepticism as European regulators decided to roll it out to seniors as well. Still, that initial delay cast a shadow over an effective shot and slowed down vaccination among vulnerable groups. 

This isn’t the first time pharmaceutical companies stumbled in the design of clinical trials, says Tit Albreht, head of the Centre for Health Care at Slovenia’s National Institute of Public Health. 

“Pharma has made the same mistake again with the vaccines,” explained Albreht, speaking at a working group roundtable organized by POLITICO. Studies need to look at “actual populations,” not just “those that are easier and safer for the managers of the trials to manage.” 

The problem: Clinical trials often include participants who are healthier than the average person who will actually take the drug once it’s approved.

On one hand, this can allow for safer trials and helps separate the effects of the drug from any complicating factors. On the other hand is the fact that in real life, patients often suffer from more than one disease at the same time. Often these illnesses are related — like cancer patients who are more at risk of cardiovascular disease because of their chemo medication. 

This is particularly true for older patients, explained Matti Aapro, an oncologist who is also president of the European Cancer Organisation. A number of complications tend to emerge with age: Kidney function starts to fail, muscle mass decreases, and the body becomes less able to metabolize certain drugs 

This shouldn’t lead to a blanket exclusion of patients from clinical trials or leaving them untreated, he added. But “you have to adapt the reality of the drugs to these factors,” he noted.

You never stop learning 

One solution is to continue gathering data on how a drug is working even after it enters the market. 

That’s what Belgium is doing, notes Diane Kleinermans, president of the Commission of Drugs Reimbursement for the National Institute for Health and Disability Insurance. She points to agreements struck with pharma companies that require them to keep collecting evidence on their drugs even after a reimbursement deal is signed.

Called managed access agreements, these contracts allow a drug to go on the market with the proviso that there’s a follow-up — for example, data on how it performs in certain at-risk groups like the elderly, who might not have been sufficiently included in the original study. The medicine’s indication and reimbursement can then be adjusted after the data has been collected. 

These deals also help ensure that payers like insurers or national health bodies get the most for their money when “you have a limited budget,” Kleinermans explained. 

In Belgium, a real-world evidence initiative —called RWE4Decisions — was created by the national social security system a year ago and has launched a number of workshops and seminars. Final conclusions are due in late 2021, with the aim of setting in place “proper guidelines with regard to real world data collection for decisions,” she said.   

The initiative also involves regulators and payers from countries like Ireland, the Netherlands and Finland, as well as the European Medicines Agency. And the broader trend toward real-world evidence is European-wide, she added.

But going from theory to reality isn’t so simple. The first agreements caused “frustration” and “disillusion,” Kleinermans noted, because companies often didn’t uphold their end of the bargain in collecting all the specified data or staying on deadline.

But now, payers are getting better at structuring the deals and making sure the infrastructure and cooperation are in place from other participants in the effort — including the busy doctors who are asked to record the data in the course of their normal workday. 

Never let a crisis go to waste

There’s one possible silver lining to the pandemic: It could actually accelerate changes in how data is collected, said Duane Schulthess, managing director at consultancy Vital Transformation. It has already forced regulators to become more flexible, and pharmaceutical companies more innovative, in his view.

Schulthess pointed to the clinical trial of the BioNTech/Pfizer coronavirus vaccine, the first shot to be approved in the U.S. and Europe, as an example, given the speed of the rollout and the monitoring that was carried out afterwards. 

“Normally you’d take several years, and there would be a longer review period on the back end,” he explained. Instead, BioNTech/Pfizer opted to conduct what was still a sizable study and then continue to monitor vaccinations closely. 

The need to fight the pandemic helped, but “many of us have been advocating this approach for many, many years,” he noted. And he believes that these kind of trials will go from being the exception to “start to become the rule,” as the approach already has backing from important figures like Hans-Georg Eichler, senior medical officer at the European Medicines Agency.

At the heart of the discussion is how to use data to figure out when drugs do and don’t work. 

Even in a successful Phase 2 drug study, a medicine might have something like a 30 percent positive response, so “we have 70 percent of the patients in the studies that are left out without any responses,” said Andrej-Franc Plesničar, senior adviser at the Health Insurance Institute of Slovenia, at the POLITICO roundtable. “So how to improve that?”

One answer is a better and more detailed understanding of the biology of the human body, and how it interacts with medicines, he believes. But that understanding needs data. Health systems generate mountains of data, but it’s not always formatted in a way that’s easily accessible for the researchers who need it. 

The Commission, for its part, has signaled that it’s taking the issue seriously. 

According to John Ryan, DG SANTE’s director for public health, cancer registries — depositories of patient data concerning the disease — “need to be substantially improved.” The Commission is working with the World Health Organization’s International Agency for Research on Cancer on that front, notes Ryan, who was responsible for creating the recently-published Cancer Plan.

The same policy document is also pushing forward data sharing through the Digital Europe program as well as the Health Data Space, he said at the POLITICO roundtable.

These initiatives “will clearly have an impact on the availability of data and how quickly it’s collected and the standards to which it’s collected,”  Ryan said. 

Other actions envisaged in the plan include a medical-imaging program that will use AI to improve diagnosis. 

But even in the midst of all of this, clinical trials aren’t going anywhere, said Kleinermans. It’s only with clinical trials that you can create a standardized setting that avoids bias. 

“The end solution will be a combination of real world data, as well as clinical trials,” she said. 

This article is produced with full editorial independence by POLITICO reporters and editors. Learn more about editorial content presented by outside advertisers.

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