Re­searchers find 15% of tri­als could be repli­cat­ed us­ing re­al world da­ta

A study pub­lished this week in JA­MA Net­work Open finds that cur­rent­ly avail­able re­al-world da­ta (RWD) sources can on­ly be used to fea­si­bly repli­cate 15% of clin­i­cal tri­als.

The aim of the study was to de­ter­mine whether RWD could be used to pow­er ob­ser­va­tion­al stud­ies that an­swer the same clin­i­cal ques­tions as tra­di­tion­al clin­i­cal tri­als.

Ran­dom­ized con­trolled tri­als (RCTs) are con­sid­ered the gold stan­dard for clin­i­cal ev­i­dence to sup­port the safe­ty and ef­fi­ca­cy of med­ical prod­ucts due to high lev­els of in­ter­nal con­sis­ten­cy and re­duced bias.

How­ev­er, as the au­thors of the study write, “Com­pared with RCTs, RWE [re­al-world ev­i­dence] bet­ter re­flects the ac­tu­al clin­i­cal en­vi­ron­ments in which med­ical in­ter­ven­tions are used, in­clud­ing pa­tient de­mo­graph­ics, co­mor­bidi­ties, ad­her­ence, and con­cur­rent treat­ments,” not­ing that RCTs are cost­ly and time in­ten­sive com­pared to ob­ser­va­tion­al stud­ies.

To con­duct the study, the au­thors re­viewed 220 clin­i­cal tri­als con­duct­ed in the US that were pub­lished in the top sev­en med­ical jour­nals in 2017 and de­ter­mined whether RWD ob­tained from in­sur­ance claims and elec­tron­ic health records (EHRs) con­tained the in­for­ma­tion nec­es­sary to repli­cate the stud­ies.

Of those tri­als, the au­thors were on­ly able to iden­ti­fy 86 (39%) that “had an in­ter­ven­tion that could be as­cer­tained from in­sur­ance claims and/or EHR da­ta.” From there, the au­thors nar­rowed the tri­als fur­ther to iden­ti­fy ones with an in­di­ca­tion and in­clu­sion/ex­clu­sion cri­te­ria that could be ex­tract­ed from RWD.

From there the au­thors were able to iden­ti­fy just 33 (15%) tri­als with one or more pri­ma­ry end­points that could be as­cer­tained from avail­able RWD sources.

“This find­ing sug­gests the po­ten­tial for re­al-world ev­i­dence to com­ple­ment clin­i­cal tri­als, both by ex­am­in­ing the con­cor­dance be­tween ran­dom­ized ex­per­i­ments and ob­ser­va­tion­al stud­ies and by com­par­ing the gen­er­al­iz­abil­i­ty of the tri­al pop­u­la­tion with the re­al-world pop­u­la­tion of in­ter­est,” the au­thors write.

How­ev­er, the au­thors cau­tion that for new prod­ucts, RWE is un­like­ly to serve as a re­place­ment for RCTs and point out that many of the tri­als they looked at could not be repli­cat­ed be­cause the da­ta nec­es­sary to do so “are un­like­ly to ap­pear in an EHR in struc­tured form if at all.”

But the au­thors stress that RWE could be used to pro­vide “crit­i­cal in­sights” in­to prod­uct safe­ty and ef­fi­ca­cy in the postap­proval set­ting and could al­low the FDA to iden­ti­fy and act on safe­ty is­sues more quick­ly.


RAPS: First pub­lished in Reg­u­la­to­ry Fo­cus™ by the Reg­u­la­to­ry Af­fairs Pro­fes­sion­als So­ci­ety, the largest glob­al or­ga­ni­za­tion of and for those in­volved with the reg­u­la­tion of health­care prod­ucts. Click here for more in­for­ma­tion.

Tal Zaks, Moderna CMO (Moderna via YouTube)

UP­DAT­ED: NI­AID and Mod­er­na spell out a 'ro­bust' im­mune re­sponse in PhI coro­n­avirus vac­cine test — but big ques­tions re­main to be an­swered

The NIAID and Moderna have spelled out positive Phase I safety and efficacy data for their Covid-19 vaccine mRNA-1273 — highlighting the first full, clear sketch of evidence that back-to-back jabs at the dose selected for Phase III routinely produced a swarm of antibodies to the virus that exceeded levels seen in convalescent patients — typically in multiples indicating a protective response.

Moderna execs say plainly that this first stage of research produced exactly the kind of efficacy they hoped to see in humans, with a manageable safety profile.

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Tillman Gerngross, Adagio Therapeutics CEO

An­ti­body leg­end Till­man Gern­gross is el­bow­ing his way in­to the Covid-19 R&D cru­sade: 'I don’t see this end­ing any­time soon'

One of the most influential — and outspoken — scientists at work in the field of antibody discovery is jumping into the frenzied race to create new therapeutics to treat and prevent Covid-19. And he’s operating with the conviction that the current outbreak now once again spreading like wildfire will create plenty of demand for what he has in mind.

Dartmouth professor and Adimab CEO Tillman Gerngross tells me he’s raised $50 million from a group of close VCs to spin out a new company — Adagio Therapeutics — with a full C-suite team assembled to hire up a staff and keep rolling toward the clinic.

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Trans­port Sim­u­la­tion Test­ing for Your Ther­a­py is the Best Way to As­sure FDA Ex­pe­dit­ed Pro­gram Ap­proval

Modality Solutions is an ISO:9001-registered biopharmaceutical cold chain engineering firm with unique transport simulation capabilities that support accelerated regulatory approval for biologics and advanced therapeutic medicinal products (ATMP). Our expertise combines traditional validation engineering approaches with regulatory knowledge into a methodology tailored for the life sciences industry. We provide insight and execution for the challenges faced in your cold chain logistics network.

Norbert Bischofberger, Kronos CEO

Gilead­'s ex-R&D chief Bischof­berg­er heads back to the biotech gi­ant to pick up a pair of late-stage drugs that had been put aside

Norbert Bischofberger knows entospletinib well.

Back during his long, blockbuster run as head of R&D at Gilead, researchers had once held some high hopes for this drug. But to make it work, he and the team felt it would need a new companion diagnostic to identify patients. There was talk of a combo approach to give it more punch. But the market was small, making them wonder if it would be worth going through a lengthy development cycle to get it through a pivotal.

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The $1B Mer­ck-Bay­er drug that di­vid­ed car­di­ol­o­gists in March gets pri­or­i­ty re­view

Three months after Merck published in the New England Journal of Medicine data that left doctors and investors divided over just how well its experimental heart drug worked, the FDA has handed that drug priority review. A decision is now due by January 20, 2021.

Merck first announced the drug, known as vericiguat, as a Phase III success last November. In 2016, Merck had paid $1 billion upfront for US rights to the Bayer-developed drug. Early projections foresaw a few hundred million a year in sales, but the unspecified late-stage success raised the possibility for far more. After all, Novartis’s flagship heart drug, Entresto, was earning $1.7 billion per year and was expected to reach up to $4 billion in annual sales.

GSK’s Shin­grix leader Guil­laume Pfe­fer has jumped on board Flag­ship to helm a biotech hy­brid as Afeyan’s lat­est CEO-part­ner

After spending 4 years in a senior post with GlaxoSmithKline’s star team positioning Shingrix for a blockbuster approval, Guillaume Pfefer is headed back to the biotech world — in style.

Pfefer has signed on to join Noubar Afeyan’s busy group of partners at Flagship, and he’s taking the helm of an upstart — which today is being merged with another Flagship startup — with some grand plans of its own. The announcement this morning notes that Pfefer will run Kintai Therapeutics, one of the grads of the Flagship labs.

Donald Trump and Anthony Fauci (AP Images)

Covid-19 roundup: Rus­sia hack­ers tar­get US,UK vac­cine and drug re­searchers; Fau­ci fires back at White House cam­paign to un­der­mine him

Russia has tried to steal Covid-19 vaccine and therapeutics researcher from pharmaceutical and academic institutions in the US, UK and Canada, Britain’s National Cyber Security Centre said Thursday.

The NCSC said that hacking attempts came from a group known as APT129, also known as also known as ‘Cozy Bear,’ that “almost certainly operate as part of Russian intelligence services.” The Canadian Communication Security Establishment, US Department for Homeland Security, the Cybersecurity Infrastructure Security Agency, and the National Security Agency shared the assessment, the NCSC said.

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John Furey, Imvax CEO

A neu­ro­sur­geon spent the past 30 years de­vel­op­ing a neoanti­gen tu­mor vac­cine. Now he has $112M for a piv­otal test

As a neurosurgeon, David Andrews knew there wasn’t much he could do for his glioma patients after resecting — rarely fully — their tumor. Even with the best treatment and care available, median overall survival is just somewhere between 14 and 16 months.

Then in the 1990s, his mentor at Thomas Jefferson University introduced him to Renato Baserga, a pathologist who had been studying the effect of using antisense oligonucleotide to knock out the insulin-like growth factor type 1 receptor in cancers. As IGF-R1 drives tumor growth and metastasis, the preclinical reasoning went, implanting a molecule targeting the receptor together with the tumor material near lymph nodes can slow down the spread of the cancer.

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Who are the women blaz­ing trails in bio­phar­ma R&D and lead­ing the fight against Covid-19? Nom­i­nate them for End­points' spe­cial re­port

One of the many inequalities the pandemic has laid bare is the gender imbalance in biomedical research. A paper examining Covid-19 research authorship wondered out loud: Where are the women?

It’s a question that echoes beyond our current times. In the biopharma world, not only are women under-represented in R&D roles (particularly at higher levels), their achievements and talents could also be undermined by stereotypes and norms of leadership styles. The problem is even more dire for women of color.